Sunday, December 25, 2011

Holiday Wishes to you All !! Melanoma..Jim Breitfeller

I would like to wish each and every one of my carepage friends the warmest and deepest greetings this Holiday Season. We been through a lot and with the comfort of family and friends we can beat the Beast Melanoma.

It has been truely a renewed emergence in Melanoma therapy this past year with TWO therapies being FDA approved that extends survival for us Melanoma patients. At this time of the Season, please relect on the Worriors that are no longer with us, but made this all possible by offering their life to the progress of science.

They truely have shown us the gift of giving.

They truely are my/our HEROS!!!

We will miss them dearly.

Happy Holidays

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”

~Charles Darwin~

Take Care,

Jimmy B


Wednesday, December 14, 2011

'Pep talk' can revive exhausted immune cells: Study..Melanoma..Jim Breitfeller

'Pep talk' can revive exhausted immune cells: Study
Published: Wednesday, Dec 14, 2011, 14:33 IST
Place: Washington, DC | Agency: IANS

'Pep talk' can revive exhausted immune cells

Exhaused immune cells can be revived by blocking the receptors PD-1 on the The CD8+ T-cells. By reviving the immune cells (CD8+), one can jump start the immune system and may be able to recognize the Melanoma tumors. There are now a number of clinical trials with this therapy in mind.

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”

~Charles Darwin~

Take Care,

Jimmy B


Monday, December 5, 2011

Lloyd J. Old, Champion of Using Cells to Fight Cancer, Dies at 78..Melanoma..Jim Breitfeller

Lloyd J. Old, Champion of Using Cells to Fight Cancer, Dies at 78

My theory on how the immune system works on Melanoma had it's starts with papers from Dr. Lloyd Old.

Lloyd J. Old, Champion of Using Cells to Fight Cancer

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”

~Charles Darwin~
Take Care,

Jimmy B

Thursday, October 20, 2011

Why Does Yervoy need to be systematically combined with IL-2? Melanoma..Jim Breitfeller

Yervoy therapy acts upon the T-cells by blocking the CTLA-4 receptor, making it unable to engage. By doing this blockade, the CD28/B7 complex can engage and the signaling to activate, secrete and multiply is allowed. Cytokines produced by activated cells can stimulate or inhibit the production of other cytokines by the same cells in an autocrine manner or those present in the vicinity by a paracrine mechanism. Thus, a complex network of cell interactions is established, with positive and negative feedback controls, regulating cytokine production. For example,
TNF-a induces the synthesis of both IL-1 and IL-6 in macrophages. In contrast, IL-10, which is also synthesized by macrophages, inhibits the synthesis of TNF-a, IL-1 and IL-6. Both IFN-g and TNF-a can activate macrophages, which subsequently synthesize TNF-a and IL-1. What I am trying to elude to is that depending on the microenvironment which contains many cytokines, the pattern of cytokines matters whether the macrophages are activated or not.

This does not take into account the suppressiveness of the Tumor’s activity. Melanoma tumors can secrete TGF-b and IL-10 and other suppressive molecules. These suppressive cytokines (IL-10) can block the activation of the tumor associated macrophages (TAMs) which in turn inhibits the secretion of other cytokines and chemoattractants into the Tumor’s microenvironment. This inhibition suppresses the “Danger Signal” needed to alarm the immune system of foreign invaders (Tumor cells).
Th1 cells promote macrophage activation by producing IL-2 and IFN-g. What if the Th1 cells are not producing enough or there are many Tregs in the tumor’s microenvironment recruited by the tumors themselves? The Tregs, Th1 and the CD8+ T-cells are all competing for the IL-2 for survival. There could be a shortage of IL-2 to satisfy all the cells leading to a less than robust response. It has been greatly accepted that macrophage activation by IL-2 is essential for tumor regression. et al Masztalerz
So administration of HD IL-2 during the peak propagation of the (ALC) Absolute Lymphocyte Count (7 weeks or 49 days) may be synergetic to Yervoy.

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”

~Charles Darwin~
Take Care,

Jimmy B


Friday, October 14, 2011

Identifying and Over Coming Immune Barriers at the Level of the Tumor Microenvironment..Melanoma .Jim Breitfeller

Eleventh International Conference on Progress in Vaccination Against Cancer

Dr. Thomas Gajewski
University of Chicago,Chicago,IL,USA

"Immunotherapeutic approaches for the treatment of melanoma, such as tumor antigen-based vaccines, can frequently boost immune responses. However, clinical responses as measured by tumor shrinkage are seen in only a minority of patients. This observation has prompted careful analysis of the tumor microenvironment for biologic correlates to clinical response and also to identify mechanisms of tumor resistance. Patients with advanced melanoma treated with antigen-specific vaccines had pre-treatment tumor biopsies analyzed by gene expression profiling. Supervised hierarchical clustering was performed based on clinical outcome. An expanded bank of tumors was analyzed to increase the sample size and better understand gene patterns.
Two major categories of melanoma metastases have been observed.

One subgroup of patient has an inflamed phenotype that includes expression of chemokines, T-cell markers, and other immunoregulatory factors. Clinical responders to melanoma vaccines appear to fall within this subset. This group also contains the highest expression of negative regulatory factors, including PD-L1, IDO, and FoxP3, suggesting that these immunosuppressive mechanisms may dominantly inhibit anti-tumor –cell function in those patients. In addition, absence of B7 expression supports classical T-cell anergy. Preclinical experiments have confirmed a critical role for these mechanisms in limiting anti-tumor T–cell efficacy in vivo, giving candidate treatment strategies for translation back into the clinic.

A second subset of patients is represented by tumors which are non-inflamed and lack chemokines for T cell recruitment. Therefore, a major barrier in these cases appears to be failed T –cell migration into tumor sites. Experimental strategies to augment T-cell migration can have important anti-tumor effects in preclinical models. The presence of the "inflamed" gene signature was associated with a type I IFN transcriptional profile, and murine experimental models have confirmed a critical role for type I IFN signaling in promoting adaptive immunity."

So,In the first subset, tumors had a suppresive nature that may be over riddden by Anti-CTLA-4 (Yervoy) and or Anti-PD-1 Therapy

The second subset was missing the "danger signal" inflammatory cytokines and chemoattractants most likely due to STAT3 signaling from the Tumor.

Stimulation of Toll-like receptor 4 (TLR-4) activates macrophages and results in the release of TNF-alpha. It is hypothesized that melanoma inhibits macrophage activation by suppressing TLR-4 signaling.

Cytokines are small proteins which allow cells of the immune system to communicate with one another via cytokine receptors expressed at the cell surface.
Activated macrophages defend against tumors by secreting cytokines to recruit secondary immune cells, presenting antigen to T cells, and by direct tumor cytotoxicity. Peritoneal macrophages harvested from melanoma-bearing mice are less cytotoxic to melanoma cells, and produce less superoxide, nitric oxide, and tumor necrosis factor-alpha (TNF-alpha) than those from nontumor-bearing mice. Similar impairment of macrophage activation occurs in vitro using media harvested from cultured melanoma cells.

Activated Macrophages secrete the following cytokines under different conditions:
IL-1,IL-12,IL-6, IFN-gamma/alpha/beta and TNF-alpha


Interleukin 6 is a pro-inflammatory cytokine and is produced in response to infection and tissue injury. IL-6 exerts its effects on multiple cell types and can act systemically.

IL-6 stimulates liver secretion of acute phase proteins
IL-6 stimulates B-lymphocytes to produce antibodies
IL-6 in concert with IL-1b causes T-cell activation
IL-6 induces STAT 3 Signaling
IL-6 Plus TGF-b induces the Th17 cell phenotype

IL-1 beta

Interleukin-1b is a pro-inflammatory cytokine which is secreted by macrophages activated by a number of stimuli including TNF-alpha, bacterial endotoxin and IL-1b itself.
IL-1b exerts its effects on many different cell types locally at the site of production and systemically (at a distance).


Interleukin-12 is a heterodimer consisting of a p35 and a p40 subunit. Both subunits are required for receptor binding and biological activity.
IL-12 stimulates growth of activated Natural Killer (NK) cells, CD8+ and CD4+ T- cells.
IL-12 increases NK and T-cell g-IFN production which shifts T-cell differentiation towards a Th1-type response.
IL-12 increases NK production of TNF-alpha which can act synergistically with IFN-gamma.
IL-12 suppresses IL-4 induced IgE production.


Tumor Necrosis Factor alpha is made by many other cells as well as macrophages, which are major sources, especially after priming by Interferon gamma.
TNF-alpha initiates a cascade of cytokines which mediate an inflammatory response. TNF-alpha effects are mediated through two types of receptor, a 75kDa TNFR-a receptor and a 55kDa TNFR-b receptor.
TNF-alpha regulates the expression of many genes in many cell types important for the host response to infection.


Macrophages, and many other cells produce these Type I interferons which act as immunomodulatory, as well as antiviral cytokines. Distinct receptor from interferon gamma, mediates overlapping or competing effects on macrophages. Cellular signalling pathways involve Jak/Stats, and other pathways.

So, if Melanoma suppresses Macrophage Activation, then the tumor microenviroment is missing IL-6, IL-1b and other cytokines.

If you look at the above micrographs, you will see that the two patients that had relapsed (10710 and 10737) Had IL-1b and IL-6 missing. The macrophages were not activated!!!! The "Danger Signal" known as inflammation was missing!

The missing combination of IL-1 and IL-6 meant there is no T-cell activation. And no induction of the Th17 phenotype. It is now becoming a lot more clearer based on Dr. Gajewski's findings.

Now might be the time for a critical re-evaluation of our overall approaches to targeting STAT3 and for developing new models for disrupting the protein in order to accomplish the goal of delivering clinically useful direct STAT3 inhibitors as novel anticancer agents in a timely manner.

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”

~Charles Darwin~
Take Care,
Jimmy B


Monday, October 3, 2011

MedImmune Inks Deal for Pfizer's Anticancer mAb Therapeutic..Melanoma .Jim Breitfeller

MedImmune inked an in-license agreement with Pfizer for tremelimumab, a mAb therapeutic for various types of cancer. Pfizer presented final toxicity results of a Phase I dose-escalation trial of tremelimumab in combination with gemcitabine in chemotherapy-naive patients with metastatic pancreatic cancer.

Under terms of the deal MedImmune will assume global development rights to tremelimumab. Pfizer retains rights to use the drug compound with specified types of combination therapies.

Pfizer previously signed over developments rights covering tremelimumab in melanoma to Debiopharm after the mAb failed in a Phase III melanoma trial. The interim analysis found that it would not offer any benefit over standard chemotherapy. Thus in April 2008, Pfizer was forced to halt the trial.

A full evaluation of the data revealed a biomarker that predicted patients who were more likely to respond, according to Pfizer. Debiopharm will be responsible for conducting a new Phase III study that leverages this marker to select patients with unresectable, stage IV melanoma. At the time of inking the deal with Debiopharm, Pfizer said it would retain all commercial rights.

Tremelimumab is a fully human mAb that binds to the protein CTLA-4, expressed on the surface of activated T lymphocytes. "Adding another immunotherapeutic approach to our oncology pipeline, one which may employ the immune system itself to fight cancer, exemplifies our continued commitment to embracing this new era of cancer care," says Bahija Jallal, Ph.D., MedImmune's evp, R&D.

MedImmune has seven clinical-stage mAb programs for cancer treatment. Phase I candidates bind to CEA and CD3, CD22, IGF, CD19, and Ang2. The Phase II candidate targets PDGFRα and is being tested in lung cancer and glioblastoma. The company believes that the platelet-derived growth factor receptor alpha (PDGFRα) pathway, with its potential role in regulating transformation as well as tumor microenvironment, progression, and metastasis, may be an important cancer target.

MEDI-575 is a fully human mAb to PDGFRα being tested in lung cancer. It has been shown to inhibit signaling from PDGFRα on cancer cells and supportive stroma. However, MEDI-575 reportedly does not inhibit PDGFRβ, the inhibition of which has been associated with significant clinical toxicities including extravascular fluid accumulation.

MEDI-575 is a fully human mAb to PDGFRα being evaluated as a treatment for glioblastoma multiforme. MEDI-575 has been shown to inhibit signaling from PDGFRα on cancer cells and supportive stroma but not PDGFRβ, MedImmune says

Bristol Myer Squibb will now be looking in the rearview mirror and seeing MedImmune in it. Down the road we may see the price of these anti-CTLA-4 antibodies go down.


This is becomming Very Intersesting!!!

A race for the CURE!!!!!

It is good to see some Competition.

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”

~Charles Darwin~

Take Care,

Jimmy B


Wednesday, September 28, 2011

The Anti-PD-1 Therapy Race for Approval by the FDA is On..Melanoma ..Jim Breitfeller

When it rains, it pours!!!! Melanoma patients over the last twenty years have not seen any progress in the fight to cure Melanoma. That has all changed in 2011 when the FDA approved Yervoy (Ipi..Ipilimumab), an anti-CTLA-4 monoclonal antibody and Zelboraf (vemurafenib). Well, this all going to change Melanoma from a cancer to a chronic disease that may be stabilized or even cured. The new Kid on the block( PD-1) is another Surface molecule that is unregulated when the T-cells are activated. This molecule is time dependent , which means that over time it migrates to the surface. Base on the research today, PD-1 molecule causes global inhibition to activated T-cells and down regulates the IL-2 expression by the PI3K/Akt pathway. It also inhibits the ICOS molecule that is an important co-stimulator for the T-cells.

So with stakes high to be the first to market, Bristol Myer Squibb, a little known company, Amplimmune, co-sponsored by GlaxoSmithKline and Curetech, a subsidiary of Teva Pharma of Israel are in the race of their lives. Winner takes all. And to throw Icing on the cake, the blockage of both inhibitors (PD-1 and CTLA-4) have shown remarkable ability to eradicate Melanoma tumors in mice.

Bristol Myer Squibb seems to be leading this race with a clinical trials recruiting at Sloan Kettering in New York and Yale in Connecticut.

The study is “Dose-escalation Study of Combination BMS-936558 (MDX-1106) and Ipilimumab in Subjects With Unresectable Stage III or Stage IV Malignant Melanoma”
Trial: NCT01024231

So with this in mind, if was seeking to try a clinical trial at this time, I would seek out the combination first, then PD-1 and if all else fails, Anti-CTLA-4 therapy followed by IL-2.

I see a Stabilization/Cure on the horizon for this disease and others based on these immunotherapies.

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”
~Charles Darwin~
Take Care,
Jimmy B


Monday, September 26, 2011

Why Is Interleukin-2 so important for mounting an immune response?.Melanoma..Jim Breitfeller

The T-cell-specific cell-surface receptors CD28, CTLA-4, ICOS and PD-1 are important regulators of the immune system. CD28 potently enhances those T-cell functions that are essential for an effective antigen-specific immune response, and the homologous CTLA-4 counterbalances the CD28-mediated signals and thus prevents an otherwise fatal overstimulation of the lymphoid system. PD-1 engagement can prevent ICOS but not CD28 costimulation. The inability of ICOS costimulation to override PD-1 inhibition is directly related to the low IL-2 levels it induces upon its engagement. ICOS Costimulation requires IL-2 and can be prevented by CTLA-4, PD-1 engagement. With the CD3/CD28 blocked downstream at the P13K and the Akt pathways, the T-cell is activated but the proliferation and survival of T-cells/immune response is terminated.

A picture is worth a thousand words.

Based on the above model, Downstream of the CD3/CD28 signaling the co-inhibitors down modulate the P13/Akt signaling. Signaling via CD28 is required for optimum IL-2 production, cell cycle progression, and survival. CD28 is constitutively expressed on naive CD4+ T cells is slightly upregulated after T cell activation.

The CTLA-4 and the PD-1 expression increase over time in Melanoma patients. This is why it is so very hard to eradicate Melanoma in the late stage IV.

To counteract the inhibition, one can use Antibodies to block the suppressive signaling coming from the CTLA-4 and PD-1. This is where Yervoy (Anti-CTLA-4) and Anti-PD-1 come into play. So if you can do a therapy with a systematic approach, you may be able to beat Melanoma.
It is now known, that IL-2 can down regulate PD-1 receptor so you might not need to do Anti-PD-1 therapy. Or you might do anti-PD-1 instead of IL-2 therapy to cut down the harsh effects of the IL-2 therapy. It is now known that the T-cell activation/immune response needs IL-2 to produce a robust immune response.

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”

~Charles Darwin~

Take Care,

Jimmy B


Friday, September 23, 2011

Ultimate fate of cellular immune responses is determined by the balance between positive & negative signals delivered by T-cells..Melanoma ..Jim Breit

ICOS Expression,To secrete and what to secrete is the question.

My research has taken me to the costimulators and coinhibitors of the T-cell activation. The Delicate balance between the costimulators and coinhibitors render the right immune response at the right time. One of these costimulators is the ICOS. But if there is to much ICOS, then there is a down regulation of the the immune response by the secetion of IL-10 into the tumor's microenviroment.

The level of ICOS surface expression regulates the magnitude of the in vivo Th1/Th2 ratio, perhaps by influencing Th2 differentiation. This regulation plays a major role in the differentiation of the T-cells.

The linkage between low ICOS expression and “early” cytokines, and between intermediate/high ICOS expression and “late” cytokines is intriguing and could mean that ICOS is gradually up-regulated in the course of progressing T cell differentiation.

ICOS-low-cells were found to be loosely associated with the early cytokines interleukin (IL)-2, IL-3, IL-6, and interferon (IFN)-gamma.

ICOS-medium cells, the large majority of ICOS_ T cells in vivo, were very tightly associated with the synthesis of the T-helper type 2 (Th2) cytokines IL-4, IL-5, and IL-13, and these cells exhibited potent inflammatoryeffects in vivo.

In contrast, ICOS-highT cells were highly and selectively linked to the antiinflammatory cytokine IL-10.

The strength of the effector response of Th cells is regulated by the control of ICOS expression.

Overall, this data seem to indicate that ICOS cell surface density serves as a regulatory mechanism for the release of cytokines with different immunological properties.

We want the low expression of ICOS which seems to differeniate the niave T-cells towards the TH1 T-cell phenotype. We can accomplish that with Yervoy (Anti-CTLA-4). STAT5 signaling is found in both the Th2 and Treg pathway.It just so happens Yervoy causes the phosphorylation of STAT5 to decreased significantly with increasing concentrations . Yervoy skews the T-cell differentiation towards the Th1/Th17 phenotype which we want.

Another coinhibitor which surpresses the immune resonse is (PD-1) Program Death 1.

Blockade of PD-1 by monoclonal antibodies specific to its ligands (PD-L1 and PD-L2) results in significant enhancement of proliferation and cytokine (gamma interferon [IFN-gamma] and interleukin-2 [IL-2]) secretion by tumor-specific CTLs. PD-1 blockade also resulted in down-regulation of intracellular FoxP3 expression by Tregs.

So by do a combinatorial therapy with Yervoy and PD-1 antibodies, It would most likely have a synergistic immune response.

This why on 9-20-2011, Bristol Myer Squibb expanded it's deal with Japan's Ono Pharmaceutical Co. Ltd. BMS now knows that they have an monopoly on T-cell activation and can be applied to many other cancers besides Melanoma. They are collecting the "String of Pearls". It would not surprise me they will go after the rest of the costimulators and coinhibitors on the T-cells. Only time will tell.

My hope is that Bristol Meyer Squibb uses it for the cure of cancer one day and not just monetary gains.

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”
~Charles Darwin~
Take Care,
Jimmy B

Friday, August 26, 2011

How does Ipilimumab (Yervoy) work? Melanoma..Jim Breitfeller

Ipilimumab is anti-CTLA-4 monoclonal antibody.

Ipilimumab C6742H9972N1732O2004S40
immunoglobul has a calculated molecular formula of C6472H9972N1732O2004S40 and a molecular weight of 145.4 G1, anti-(human CTLA-4 (antigen)) (human gamma1-chain), disulfide with human kappa-chain, dimer [CAS] immunoglobulin G1, anti-(human CTLA-4 (antigen)) (human g1-chain), disulfide with human k-chain, dimer [CAS]

Half Life = 15 days

Tremelimumab (from Pfizer) is an IgG2
Tremelimumab is a fully human cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) IgG2 monoclonal antibody, presumably manufactured using transformed mammalian cells. Tremelimumab is a dimer (composed of two chains) linked by a disulfide/sulfhydryl bond. Tremelimumab has a calculated molecular formula of C6500H9974N1726O2026S52 and a molecular weight of ~150 kDa

Half life= 21 days

In T-cell activation, the receptor, CTLA-4 is upregulated on about day 3.

The CTLA-4 complex can suppress the immune response.

CTLA-4 that interferes with Dendritic cell (DC) costimulation via reduced CD80/CD86, (B7-1-2) expression and CD25 (IL-2 receptor) to allow for Treg survival, activation, and effective competition for limited IL-2 during infection.

Ipilimumab (Yervoy) works by blocking the CTLA-4/ B7-1/2 complex, which allows the costimulation of the CD28// B7-1/2 complex to take place. This takes the brakes off the immune response allow the response to go unchecked.

Another thing Yervoy does is that it decreases the signaling of STAT5 with increasing concentrations. That is why the best overall concentration is 10mg/Kg.

Phosphorylation of STAT5 decreased significantly with increasing concentrations of tremelimumab/Ipilimumab in monocytes from five healthy donors and from three patients with melanoma. Overall, these data demonstrate that monocytes express mostly intracellular CTLA4 and that CTLA4 is biologically active in this cell subset since exposure to tremelimumab/ipilimumab induces changes in intracellular signaling molecules.
By decreasing the signaling of STAT5 during Cell differentiation, TH17 and TH1 cells are mostly produced.

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”
~Charles Darwin~
Take Care,
Jimmy B


Tuesday, August 9, 2011

FDA approval of Roche melanoma drug (Vemurafenib) may come early

Reuters) - Regulators are moving quickly with Roche's application for targeted melanoma drug vemurafenib, which could receive approval as early as this week, according to a source familiar with the situation.

Vemurafenib, whose brand name is Zelboraf

Source: FDA approval of Roche melanoma drug may come early

Your tumors must be BRAFV600E positive

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”

~Charles Darwin~

Take Care,

Jimmy B


Sunday, July 17, 2011

Melanoma International Foundation Exposed!!!! Melanoma ..Jim Breitfeller

In the last couple of days I have been comunicating with a caregiver on the subject of Help! Interleukin-2 or Yervoy?? (lauram)Posted: 1:38:56 pm on 7/15/2011

As I went into my posts I linked some papers that I wrote on the subject matter. It was based on years of research and I thought it had some added value to the subject.

"Based on my interpretation of the science, I would do Ipilimumab (Yervoy) first. Make sure you have your ALC (Absolute Lymphocyte count) tested before the trial. If it doubles by week 7, you are most likeely a responder. If not, do the HD-IL-2 regime. Here is a paper that may help you understand the science behind the treatment."

Well, I was in great disbelief that Catherine Poole, the President and Founder of the Melanoma International Foundation had deleted my link and said

Re: Help! Interleukin-2 or Yervoy?? (Catherine Poole)
Posted: 12:24:21 pm on 7/16/2011 Modified: 12:27:43 pm on 7/16/2011


I don't think this is based on "the science" but more your opinion on the science. It just hasn't been proved in enough of the population to warrant the recommendation. We must be careful in these assumptions we make. So please do not suggest that here to patients without ample evidence in large segment of the population. We had to edit out your link since it appeared to be a virus within it."

I contunued to post links to clinical data that backed up the science.

Re: Help! Interleukin-2 or Yervoy?? (jimmy_b)
Posted: 8:57:41 pm on 7/16/2011 Modified: Never

Catherine, if you read my intial post: I said"

Based on the science, I would do Ipilimumab (Yervoy) first. Make sure you have your ALC (Absolute Lymphocyte count) tested before the trial. If it doubles by week 7, you are most likeely a responder. If not, do the HD-IL-2 regime. Here is a paper that may help you understand the science behind the treatment."

I am saying the what you are. Do Yervoy first. If you fail, then try HD IL-2. A response from IL-2 can be durable and long lasting (Over 10 Years in some cases)

Patient information:Melanoma treatment; advanced or metastatic melanoma

Author Jeffrey A Sosman, MD


Treatment of metastatic melanoma focuses on:

Shrinking or getting rid of metastases

Preventing the disease from spreading

Keeping you comfortable

In most cases, it is not possible to completely eliminate or cure the cancer. Depending upon where and how big the metastases are, treatment may involve drug treatments, surgery, or radiation therapy.

Drug treatments — There are three main categories of drug treatments:

Immunotherapy – drugs that work with your immune system to stop or slow the growth of cancer cells

Chemotherapy – drugs that stop or slow the growth of cancer cells by interfering with their ability to divide or reproduce themselves

Molecularly targeted therapy- drugs that act to inhibit specific pathways or molecules important to the cancer cells

These drug treatments may be given alone or in combination. Most of these treatments must be given into a vein (intravenously) or injected under the skin, although a few can be given in pill form. Each medication is given over a period of time, sometimes up to several months, depending upon how you respond.

Immunotherapy — Because immunotherapy works differently than chemotherapy, it has different side effects.

Interleukin-2 (IL-2) — IL-2 is a form of immunotherapy that has been found to help some people with metastatic melanoma when given in high doses. In some people treated with high dose IL-2, the benefit can be long-lasting [1-3].

However, high dose IL-2 can cause serious and toxic side effects and it is generally reserved for people who are otherwise healthy (with good heart and lung function).

IL-2 is usually given into a vein three times per day for five days twice per month. Treatment is usually completed while you are in the hospital.

Potential side effects of IL-2 — Potential side effects of high dose IL-2 include low blood pressure, irregular heart rhythms, accumulation of fluid in the lungs, fever, and rarely death.

Ipilimumab — Ipilimumab is a drug that stimulates the body’s immune system to react against the melanoma. This is given once every three weeks for a total of four doses. Treatment with ipilimumab may decrease the extent of your melanoma and help you live longer. But ipilimumab can also cause the body to develop an immune reaction against its own tissues. This can result in a wide range of side effects that may be severe or life threatening. The most important of these include colitis (causing diarrhea, bleeding, or more serious complications), hepatitis, rash or inflammation of the skin, and inflammation of endocrine organs (pituitary, thyroid, or adrenal). If this occurs, you might have to stop the ipilimumab and receive additional treatment for the complications.

If you take this drug, it is important to tell your doctor about any side effects you experience, even mild ones. This will help avoid the more serious complications.


Significant progress has been made in the treatment of metastatic melanoma over the past decade. Two drugs that stimulate the immune system, high dose interleukin-2 (IL-2) and ipilimumab, are more effective for controlling metastatic melanoma and allowing some people to live longer. However, both of these forms of immunotherapy can be associated with severe side effects.

In deciding what treatment is right for you, you and your family must consider the risks and benefits of each option according to your values and preferences."

warm regards

Jimmy B
Melanoma Missionary

Advances in Immunotherapy for the Treatment of Metastatic Melanoma

For your Information:

"THE FIRST randomized clinical trial demonstrating an effect on patient survival for the treatment of metastatic melanoma has been recently reported using the immune-stimulating antibody ipilimumab.

This is an important advance in this disease as well as a proof of concept of the ability of immunotherapy to affect the natural course of advanced melanoma. However, the objective tumor response rates are low with CTLA4-blocking antibodies. Response rates up to 50% to 70% have been achieved with an optimized combination of ex vivo, clonally expanded, tumor-infiltrating lymphocytes (TILs) administered after lymphodepleting chemotherapy and followed by high-dose IL-2 administration."

"This provides further evidence of the potential of immunotherapy for the treatment of melanoma."

Dr. Antonio Ribas 2011

My Therory, is that instead of clonally expanding the (TILs) tumor-infiltrating lymphocytes ex vivo, and not depleting the Tregs, WE are doing it all in vivo (Inside the Body). The reason we skip the Lymphodepleting is that the CD4-T-cell in need to secrete just the right amount of IL-2 to activate the and prime the CD-8 T-cells. The High dose IL-2 is there to muture the CD8- T-cells into Cytotoxic T lymphocytes (CTLs).

I know there are skeptics out there, but we need to read the research papers that are cutting edge to make any progress. Why is Dr. Steven Rosenberg using IL-2 in his ACT therapy?

You need to think outside the box and not reject things that you don't understand.
best regards

Again Catherine poole responded:

Again, Jimmy, we don't believe the science until it is proven in many individuals. Hundreds of patients should show these results before it is proven fact and enough to base an opinion about. Rosenberg has been using IL2 for 20 years or more, it is his drug of choice. Why? I'm not certain, but I've not been impressed by the results of research at NCI in melanoma. So I imagine there is funding from the industry for this particular drug to be used. And they need funding desperately for melanoma at NCI, it is not a priority. I would just suggest that our recommendations be based on large studies here and so far Yervoy has more promise than IL2 and is far less debilitating..

Catherine M. Poole, President/Founder

Melanoma International Foundation

Again I responded with :

Re: Help! Interleukin-2 or Yervoy?? (jimmy_b)
Posted: 9:58:59 pm on 7/16/2011 Modified: Never

Ipilimumab in Combination with IL-2

Author: Jeffrey Weber, M.D., Ph.D., H. Lee Moffitt Cancer Center

July of 2008

Thirty-six patients with stage IV metastatic melanoma were treated with ipilimumab at doses in the range of 0.1–3mg/kg every 3 weeks combined with IL-2 at 720,000 IU/kg every 8 hours to a maximum of 15 doses [20]. There was an ORR of 22%, with three patients having a CR and five patients having a PR. Five of the responses occurred among the 24 patients treated with ipilimumab at 3 mg/kg, and one each occurred in those treated with 0.3, 1, and 2 mg/kg. Six of the eight responders had ongoing responses at follow-up of 11–19 months. The 22% ORR reflects an additive rather than a synergistic effect for these two agents, although durable responses were demonstrated.

Based on the initial experience with ipilimumab in combination with chemotherapy or IL-2, additive effects have been seen, as opposed to synergy. However, the results from these trials suggest that combination therapy with ipilimumab may play an important role in the treatment of metastatic melanoma; larger trials are required, including an ongoing phase III trial of ipilimumab plus dacarbazine compared with dacarbazine alone in frontline therapy, before further conclusions can be drawn.

Jimmy B
Melanoma Missionary

Re: Help! Interleukin-2 or Yervoy?? (jimmy_b)
Posted: 10:35:56 pm on 7/16/2011

Cytotoxic T lymphocyte-associated antigen 4 blockade with ipilimumab: Long-term follow-up of 179 patients with metastatic melanoma 2010 ASCO Annual Meeting

Abstract No:8544

J Clin Oncol 28:15s, 2010 (suppl; abstr 8544)


P. A. Prieto, J. C. Yang, R. M. Sherry, M. S. Hughes, U. S. Kammula, D. E. White, C. L. Levy, S. A. Rosenberg, G. Q. Phan; Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; National Cancer Institute, National Institutes of Health, Bethesda, MD; National Cancer Institute, Bethesda, MD; Surgery Branch, National Cancer Institute, Bethesda, MD


Background: We have previously shown objective clinical responses in patients with metastatic melanoma treated with CTLA-4 blockade using ipilimumab. We have treated 179 patients in 3 separate clinical trials and now have long-term follow-up to evaluate the durability and unique features of this immunotherapy. Methods: A total of 179 patients with metastatic melanoma were treated in 3 trials: In Protocol 1, 56 patients received ipilimumab with gp100 peptide vaccines. In Protocol 2, 36 patients received ipilimumab with high-dose interleukin-2 (IL-2). In Protocol 3, 87 patients received intra-patient dose escalation of ipilimumab and were randomized to receive gp100 peptides. We have updated and analyzed the follow-up and survival data for these trials. Results: With median follow-up for Protocol 1, 2, and 3 being 80, 71, and 60 months, median survival was 15, 16, and 13 months, respectively. Objective tumor regression was 12% for Protocol 1, 25% for Protocol 2, and 21% for Protocol 3. Patients in Protocol 2 had a 17% complete response rate (6 patients: 77+, 74+, 72+, 71+, 71+, and 69+ months), as compared to 7% in Protocol 1 (4 patients: 82+, 81+, 79+, and 66+ months) and 8% in Protocol 3 (5 patients: 64+, 63+, 62+, 60+, and 55+ months); all complete responses are ongoing. Many patients who eventually became complete responders had continual tumor shrinkage after stopping therapy. Conclusions: CTLA-4 blockade with ipilimumab can achieve durable objective tumor regression in patients with metastatic melanoma. The combination of ipilimumab and IL-2 appears to have an increased complete response rate, although this needs to be tested in a prospective randomized trial. This report represents the largest single-institution experience with the longest follow-up for this agent; our results support its role as a viable treatment option for patients with metastatic melanoma.

Catherine My Theory does have Merit. It is the Science backup with some clinical Data.

Lets Think OUTSIDE THE BOX!!!!

best regards

Jimmy B
Melanoma Missionary

Re: Help! Interleukin-2 or Yervoy?? (Catherine Poole)
Posted: 7:10:37 am on 7/17/2011 Modified: 7:15:36 am on 7/17/2011

This just isn't the place for you to post all of this. Just give the citations. As I mentioned in the other response to your post, you are not a peer reviewed credentialled medical researcher. We always think outside the box here but we also keep in mind the validity of research and whether large numbers of people benefitted. We also talk in terms that people can understand easily. You are a missionary by your self description, bent on a mission and we are navigators exploring all options.

Catherine M. Poole, President/Founder

Melanoma International Foundation

The MIF Website and Forums are designed for educational purposes only and are not engaged in rendering medical advice or professional services. The information provided through this Website should not be used for diagnosing or treating a health problem or a disease. It is not a substitute for professional care. If you have or suspect you may have a health problem, you should consult your health care provider.

Re: Help! Interleukin-2 or Yervoy?? (Catherine Poole)
Posted: 7:12:02 am on 7/17/2011 Modified: Never

This just isn't the place for you to post all of this. Just give the citations. As I mentioned in the other response to your post, you are not a peer reviewed medical researcher.

Catherine M. Poole, President/Founder

Melanoma International Foundation

The MIF Website and Forums are designed for educational purposes only and are not engaged in rendering medical advice or professional services. The information provided through this Website should not be used for diagnosing or treating a health problem or a disease. It is not a substitute for professional care. If you have or suspect you may have a health problem, you should consult your health care provider.

Re: Help! Interleukin-2 or Yervoy?? (jimmy_b)
Posted: 8:21:51 am on 7/17/2011 Modified: Never

Catherine, What credentials do you have may I ask. How many patents do you have. I rest my case.

You are blinded by your own lack of understanding.

Jimmy B

Re: Help! Interleukin-2 or Yervoy?? (Catherine Poole)
Posted: 7:10:37 am on 7/17/2011 Modified: 10:53:34 am on 7/17/2011

This just isn't the place for you to post all of this and we don't like our forum to have the negativity that you exhibit. Just give the citations as you are taking space away from others. As I mentioned in the other response to your post, you are not a peer reviewed credentialed medical researcher. I have never claimed to be either. I rely on the opinion of medical experts who are credentialed and peer reviewed in their work in melanoma research from the outstanding cancer centers who specialize in melanoma. We always think outside the box here but we also keep in mind the validity of research and whether large numbers of people benefitted. I know you are promoting what worked for you and then backing it with research you have found that could be interpreted in a different light. We also talk in terms that people can understand easily. You are a missionary by your self description, bent on specific therapy mission and we are navigators exploring all options. You have your own website for that purpose and we'd appreciate you keeping your lengthy opinions there.

Catherine M. Poole, President/Founder

Melanoma International Foundation

This forum is moderated by specialists in melanoma, primarily by volunteer dermatologists and oncologists on a weekly basis. In addition, Catherine Poole, President and Founder of the Melanoma International Foundation, a melanoma survivor, and patient navigator for 20 years and co-author with DuPont Guerry, MD a melanoma expert, of Melanoma, Prevention, Detection and Treatment, (Yale University Press: 2005) monitors this site many times daily. Information on

Re: Help! Interleukin-2 or Yervoy?? (jimmy_b)Posted: 11:33:12 am on 7/17/2011

Re: Help! Interleukin-2 or Yervoy?? (jimmy_b)
Posted: 11:33:12 am on 7/17/2011 Modified: Never


Thanks, as you can see, Catherine Poole is pushing her own agenda and has delete my entries.

What happen to the Freedom of Speech act?

This forum is NOT moderated by specialists in melanoma, primarily by volunteer dermatologists and oncologists on a weekly basis. This is very Sad.

Jimmy B
Melanoma Missionary

If you go to Melanoma International Foundation for advice, You may not be getting the whole picture.

I was not pushing my theory, I was giving my opinion. As for Catherine M. Poole,
who is sending out The Negativity.

"We don't like our forum to have the negativity that you exhibit."
~Catherine M. Poole_

You be the judge

I don't delete links and entries or comments on my web blog. Everyone is entitled to their opinoin.

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”

~Charles Darwin~
Take Care,
Jimmy B

Thursday, July 14, 2011

After Activation With Yervoy, IL-2 Produced by Activated CD4+ T Cells Helps CD8+ T-Cell Activation.Melanoma..Jim Breitfeller

YERVOY™ (Ipilimumab) Approved For The Treatment Of Previously-Treated Advanced Melanoma In The EU
Posted 6 minutes ago
Article Date: 14 Jul 2011 - 4:00 PDT

Bristol-Myers Squibb today announced that the European Commission has approved YERVOY™ (ipilimumab) for the treatment of adult patients with previously-treated advanced melanoma.

After Activation With Yervoy, IL-2 Produced by Activated CD4+ T Cells Helps CD8+ T-Cell Activation.

IL-2 Is Critical to CD8+ T Cell Activation at Early Time Points during Priming.

combination therapy

The Action of IL-2 on CD8+ T Cells Is through IL-2 Receptor
IL-2 signals to naïve CD8+ T cells through IL2 Receptor

It is hypothesized that IL-2 may help CD8+ T cell activation through enhancing the signal that drives proliferation.

IL-2 Signaling during Priming Helps CD8+ T Cells Acquiring Effector Functions,

Generation of Potent CD8+ T Cell Anti-Tumor Effector Function Depends upon IL-2 Help.

IL-2 signal at priming drove better anti-tumor CTL function in vivo.

This is why Combinatorial Therapy is a Must to CURE Melanoma

Yervoy (Ipilimumab) + IL-2 = Melanoma CURE!!!!

You must get the tumors's microenviroment in the right configuration for it to work.

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”

~Charles Darwin~
Take Care,

Jimmy B


Tuesday, June 28, 2011

ASCO Review with Dr. John Kirkwood on Melanoma Therapies..jim Breitfeller

The full Audio of the Dr. Kirkwood interview at ASCO 2011

Please if you get a chance, listen to the full interview of Dr. John Kirkwood on the lastest therapies for Melanoma. It might help save your life or loveone's life.

Get a cup of coffee and a pad and pencil.


“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”
~Charles Darwin~

Take Care,
Jimmy B

Friday, June 24, 2011

Yervoy.. The Magic Bullet!!..Melanoma..Jim Breitfeller

Hi everyone

I´ve been reading posts at this Bulletin Board for almost a year now. Some posts I have read with tears in my eyes, and some with joy. Here is our story (short version):

I am the husband to a 39 year old woman from Denmark in Europe.

In 2003 she had a mole removed from her thigh (Stage II). It contained melanoma-cells.

In 2007 melanoma had spread to a lymph-node in her groin (Stage III). Surgery was needed.

In 2008 melanoma relapsed in another lymph-node, surgery again.

In 2009 melanoma hit us hard (Stage IV). It had spread to her lungs, one met in each lung. The size of the mets was 25 mm and 16 mm respectively. Surgery was fortunately possible.

In October 2010 melanoma went back. This time there was multiples mets in each lung. About 5-6 mets in each lung. The biggest was 19 mm. It was unsurgeable, which was very hard to cope with.

In November she began Interferon/Interleukin-2 treatment. It was tough beyond imagination. She had all the known sideeffects, and she was so bad during hospitalization. The midway PET/CT scans in January revealed that she was a responder! Scans showed that all the mets had become inactive or necrotic. Some mets had even shrunk a little bit. We were delighted, and she continued with the third and fourth series of Interferon/IL-2.

February 15 we got the results of the next scan. We were optimistic because the midway scans was indeed promising. We were shocked when told that the melanoma had began to grow again. There was 2 active mets now. One big met, about 32 mm in diameter, in her right lung lightened up. In addiction there was a lot of fluid in the right lung membrane, and it probably contained melanoma-cells. All other mets was still inactive, except one, and our doctor feared that it would be only a matter of time, before the other mets would begin to grow again. We were devastated.

Our doctor suggested Ipilimumab, and my wife started March 11, on the same day Japan was shaken by the huge earthquake. I watched it on TV while she was receiving the first dose of ipilimumab (3 mg/kg dose). I remember wishing that the drug was the earthquake of our lives…

My wife have always been a positive and happy human being, no matter what challenges life would bring, she still truly believe that she could defeat this Melanoma Devil. She began consulting a Chinese doctor and received acupuncture twice a week. Beside this she trained 4-5 times a week, fitness and running. In these situations we talked about preparing your body to fight the cancer, with a "little" help from our friend, ipilimumab…

She received 4 doses every third week and got a CT scan in June.

Three days ago on June 21 we arrived to the hospital to talk with our doctor about the results of the CT scan. The time from the scans being done and to get the results is awful with a lot of anxiety, you guys all know… The scan showed that the 32 mm met in the right lung was completely GONE!!!!! The fluid was gone too, and the x-ray showed a nice healthy looking right lung. We were stunned. I hugged my wife with a lot of tears in my eyes. Our doctor was very delighted too. Ipilimumab had worked much better than expected. We had hoped for stabilization, maybe shrinkage, if we were lucky. But this???? Unbelievable. Some other small mets was still there but hasn´t grown in size in half a year, and our doctor said it very well could be necrotic tissue.

This is where we stand now. We´re thrilled and delighted and so so happy. We have now dared to plan for more than a month :-)

So this story is to all you Warriors out there, keep on fighting with believe and trust in your hearts. The path is very tough but the battle can be won, sooner or later. We´ll keep fighting this Devil.

Kind regards



Did High Dose Interferon Alpha set the stage for the perfect Orchestration of an Immune Response?

As I continue my search for the Holy Grail, I need to keep grounding myself to what really took place in the Melanoma treatment. I can not keep wondering if Interferon therapy had played a part in our successful treatment.

Both Vicky and I did some IFN therapy first.

Vicky’s Treatment timeline:

1) Diagnosis 5/10/06
2) Excision and sentinel node biopsy 5/16/06. SN positive, MM 3.3 mm, amelanotic, ulcerated (I did just read that the ulcerated variant does seem to do well with high-dose interferon in terms of prolonging survival)
3) Elective radical lymph node dissection, right groin, 5/30/06 2 more positive lymph nodes
4) High-dose iv interferon all of July 2006, followed by subcutaneous interferon MWF for 2 months.
5) Enroll in anti-CTLA-4 study as adjuvant therapy for stage 3 MM with Dr. Jeffrey Weber at USC. First dose of intravenous infusion of anti-CTLA-4, dose of 10 mg/kg early Nov 2006, second dose was Jan. 9, 2007.
6) Chest CT, routine, for the study, was positive for bilateral pulmonary nodules on 1/18/07
7) Lung biopsy positive for MM on 2/03/07
8) First course of high-dose IL-2 was March 2007
9) 60% reduction in tumor burden on April 23 CT scans
10) Second course of IL-2 in June 2007 ( I believe I got 14 of 14 doses during the 3rd cycle or week 1 of the second course.
11) Complete response seen on CT 8/01/07
12) Took an elective 5th cycle of IL-2 in early September of 2007- got quite sick and stopped. I think I got around 9 doses that last time.

Did High Dose Interferon Alpha set the stage for the perfect Orchestration of an Immune Response?

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”

~Charles Darwin~

Take Care,

Jimmy B


Tuesday, June 14, 2011

2011 ASCO Annual Meeting Highlights on Melanoma and Neuroblastoma, with Lynn Schuchter, MD ..jim breitfeller

2011 ASCO Annual Meeting Highlights on Melanoma and Neuroblastoma, with Lynn Schuchter, MD
June 5, 2011

2011 ASCO Annual Meeting Highlights on Melanoma and Neuroblastoma, with Lynn Schuchter, MD

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”

~Charles Darwin~

Take Care,

Jimmy B


Thursday, June 2, 2011

Bristol, Roche team up on melanoma study..Jim Breitfeller

By Bill Berkrot and Lewis Krauskopf

NEW YORK | Thu Jun 2, 2011 1:30pm EDT

NEW YORK (Reuters) - Bristol-Myers Squibb and Roche Holding AG said on Thursday they would evaluate their respective cancer drugs as a potential combination therapy for metastatic melanoma.

The collaboration involves a Phase I/II study with Bristol's recently approved Yervoy and Roche's experimental drug, vemurafenib, to determine the safety and efficacy of the combination in treating the deadliest form of skin cancer.

The announcement comes as the American Society of Clinical Oncology meeting begins this weekend in Chicago, where emerging treatments for melanoma will be in the spotlight.

Among the most eagerly anticipated studies being presented at the ASCO meeting will be a Phase III trial intended to show that vemurafenib extended the lives of patients with advanced melanoma, and another study comparing Yervoy to chemotherapy in patients with the fatal disease.

Yervoy won U.S. approval in March for patients with inoperable or metastatic melanoma, making it the first new treatment option in many years for patients for whom there was little hope and virtually no effective medicines.

Roche and Japanese drugmaker Daiichi Sankyo Co recently submitted U.S. and European applications seeking approval for vemurafenib. The drug was developed by Roche's Genentech unit and Plexxikon, which was recently acquired by Daiichi.

Vemurafenib, a so-called BRAF inhibitor, is designed to selectively target and inhibit a mutated form of the BRAF protein found in about half of all cases of melanoma. The combination study with Yervoy will be in patients with BRAF-mutated metastatic melanoma, Roche said.

Roche is also developing a combination diagnostic to help identify those patients with the BRAF mutation who are likely to benefit from vemurafenib.

"We are entering a new era for melanoma, and are committed to studying exciting combinations with investigational medicines in our own pipeline," Roche Chief Medical Officer Hal Barron said in a statement.

If proven effective and approved the Yervoy-vemurafenib combination would be an extremely expensive treatment option that could meet with reimbursement resistance from government programs and health insurers.

Bristol priced a four-infusion course of Yervoy at about $120,000. Vemurafenib will likely also command premium pricing if it too demonstrates an ability to help patients live longer.

More than 70,000 people in the United States and 160,000 worldwide are diagnosed with melanoma each year, according to the American Cancer Society. The five-year survival rate for the aggressive cancer is just 15 percent.


All I can say.... It is about Time!!!! Lets all work together for the common good.

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”
~Charles Darwin~

Take Care,

Jimmy B


Wednesday, May 11, 2011

Ipilimumab and Beyond: New Therapies Imminent in Melanoma..Jim Breitfeller

Ipilimumab and Beyond: New Therapies Imminent in Melanoma
By: SUSAN LONDON, Internal Medicine News Digital Network

LAS VEGAS – Melanoma has the fastest-rising incidence of any cancer, and exacts a terrible toll among individuals who are typically in the prime of their life. But historically, it has not been a major focus in oncology, in part because of its propensity to metastasize early and the very limited treatment options when it does.

This is changing – and not just because of the landmark clinical trial showing that ipilimumab (Yervoy) can prolong the lives of these patients, Dr. Steven O’Day, a lead investigator of that trial, told attendees at the annual Community Oncology Conference

Ipilimumab targets the immune system so that it can contain the cancer, rather than targeting the tumor to eradicate the disease, explains Dr. Steven O'Day.

Four new classes of therapies are improving outcomes in patients with metastatic melanoma, according to Dr. O’Day, director of the melanoma program at the Angeles Clinic and Research Institute in Santa Monica, Calif.

The rest can be viewed at Internal Medicine News

Remember:Ipilimumab and Beyond!!!!

You heard it first back in 2006 right here. It may not be a cure, but it is a durable response that can last for YEARS!!!

With combinatorial therapy, the response rate will improve greatly.

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”
~Charles Darwin~

Take Care,
Jimmy B


Tuesday, May 10, 2011

Guess What, regulatory T cells (Tregs) control CD8+ T-cell..Melanoma ..Jim Breitfeller

Guess What, regulatory T cells (Tregs) control CD8+ T-cell
effector differentiation by modulating IL-2 homeostasis.

Research done by Raymond J. Steptoe and colleages in a paper called
"CD4+CD25+ regulatory T cells control CD8+ T-cell effector differentiation by modulating IL-2 homeostasis"

"CD4+CD25+ regulatory T cells (Treg) play a crucial role in the regulation of immune responses. Although many mechanisms of Treg suppression in vitro have been described, the mechanisms by which Treg modulate CD8+ T cell differentiation and effector function in vivo are more poorly defined. It has been proposed, in many instances, that modulation of cytokine homeostasis could be an important mechanism by which Treg regulate adaptive immunity; however, direct experimental evidence is sparse. Here we demonstrate that CD4+CD25+ Treg, by critically regulating IL-2 homeostasis, modulate CD8+ T-cell effector differentiation. Expansion and effector differentiation of CD8+ T cells is promoted by autocrine IL-2 but, by competing for IL-2, Treg limit CD8+ effector differentiation. Furthermore, a regulatory loop exists between Treg and CD8+ effector T cells, where IL-2 produced during CD8+ T-cell effector differentiation promotes Treg expansion."

By controlling the Tregs with Ipi (Yervoy)and the timing of the addition of IL-2 therapy plus IL-12 if needed, one could generate the right immune response against the Melanoma Cancer.

My theory now has all the backing of reseachers and their papers.

We need to get the oncolgists to take a look at the combinatorial therapy

Of Yervoy (Ipi), IL-12 and IL-2. This could be the major breakthrough.

The Aha Moment!!!!!

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”

~Charles Darwin~
Take Care,

Jimmy B


Researchers at UCLA's Jonsson Comprehensive Cancer Center Discover Way To Amp Up The Power Of Killer T Cells..Melanoma ..Jim Breitfeller

Researchers at UCLA's Jonsson Comprehensive Cancer Center Discover Way To Amp Up The Power Of Killer T Cells

Article Date: 10 May 2011 - 1:00 PDT

Researchers with UCLA's Jonsson Comprehensive Cancer Center have discovered a way to amp up the power of killer T-cells, called CD8 cells, making them more functional for longer periods of time and boosting their ability to multiply and expand within the body to fight melanoma, a new study has found.

The study, done in mouse models of metastatic melanoma that had spread to the brain, has important clinical implications, as the method could boost the cancer-killing power of experimental immunotherapies being tested now in various cancers, including deadly glioblastoma and metastatic melanoma, both of which are very difficult to treat successfully.

Study senior author Dr. Robert Prins, an associate professor of neurosurgery and a Jonsson Cancer Center scientist, said the killer T cells also were better able to recognize and traffic to the cancer, which is crucial as the immune system often fails to identify malignant cells as invading enemies.

The study is published in the May issue of the peer-reviewed the Journal of Immunology.

The process Prins and his team used sought to mimic the way the T cells in the immune system recognize and fight viruses in the body, stimulating what is called the innate immune system. The innate immune system is comprised of cells that immediately defend the body from infection and frequently is not stimulated in the presence of cancer, Prins said. However, the innate immune cells can be tricked into thinking a virus is present by treating with compounds that activate Toll-like receptors (TLR).

Prins' group had previously demonstrated that TLR agonists, such as imiquimod, could synergize with dendritic cell vaccines, both in mouse models and patient clinical trials. Interleukin 12 (IL-12) is one of the predominant cytokines released when TLR are activated. In this study, they wanted to see how IL-12 would affect the CD8 T cells.

Graduate student Dominique Lisiero, first author of the study, said CD8 T cells come in a large variety of "flavors" and can be stimulated in differing ways. However, what signals and which stimuli work best to prime the cells to fight cancer was unclear. Lisiero added IL-12 to the CD8 T cells in culture, before the cells were transferred into mice with established brain tumors.

"We wanted to see if we could make these cells become better at either recognizing the tumor or killing tumor cells," she said. "We didn't know what expect, but what we found was that when we programmed these cells in the presence of IL-12, we saw that the tumors decreased in size and the mice with brain metastases survived longer. In fact, Prins said that the mice treated with killer T cells primed in the presence of IL-12 lived about 2.5 times longer than those not receiving the IL-12.

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To better understand the mechanisms by which priming killer T cells in the presence of IL-12 really enhanced their function, the team focused on how these T cells responded to a different cytokine, Interleukin 2 (IL-2). IL-2, which is instrumental for the body's natural response to infection and recognition of foreign invaders, often is included in adoptive transfer immunotherapies to help the T cells survive, but it has to be given in high doses that frequently cause significant toxicity to patients. Prins and Lisiero wanted to know if adding IL-12 would enhance the sensitivity of IL-2 signaling inside the T cells.

"T cells that were primed in the presence of IL-12 had a higher expression of the IL-2 receptor, meaning the T cells had an enhanced ability to respond to the IL-2. This, we believe, allowed the killer T cells to expand and survive after being transferred into mice with brain tumors. " Lisiero said. "Because the IL-12 stimulates the IL-2 receptor, we can give much lower doses of IL-2 and still get the same anti-tumor function from the killer T cells. In patients, this may translate to reduced toxicity. Clinical trials, however, would be required to prove that this priming with IL-12 would have similar effects."

Lisiero also tested the new process on human T cells, culturing them in either IL-2 or IL-12, and studying their function in the lab. The function of the cells programmed in IL-12 was dramatically increased, Prins said, validating the work in the mouse models. Their findings are already influencing how T cells are grown in the lab, he said.

The findings also are translational to the clinic, since metastatic melanoma patients in clinical trials often are removed from the protocol when the cancer appears in their brain. Many oncologists and scientists still believe that T cells can't access the brain because of its immune privilege. This study, however, has proven in a pre-clinical model that these tumors in the brain can in fact be effectively targeted.

"The in vitro priming of mouse tumor-specific CD8 T cells in the presence of IL-12 induced a diverse and rapid anti-tumor effector activity while still promoting the generation of memory cells," the study states. "Importantly, the IL-12-primed effector T cells dramatically reduced the growth of well-established tumors and significantly increased survival to highly immune resistant, established intracranial tumors."

The study was funded by the National Institutes of Health, the Philip R. and Kenneth A. Jonsson Foundations and STOP Cancer.

UCLA's Jonsson Comprehensive Cancer Center

In my studies, If naive T-Cells differentiate in the presence of IL-12,(secreted from dendritic cells and Macrophage, the cells differentiate into the TH1 phenotype).

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”

~Charles Darwin~

Take Care,
Jimmy B


Friday, May 6, 2011

Ipilimumab is Working,, Melanoma..Jim Breitfeller

T-cell Activation!!!!!! Ipilimumab (Yervoy) is working!!!

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”

~Charles Darwin~
Take Care,

Jimmy B


Thursday, May 5, 2011

Dear 16 year Old Me.. Melanoma ..Jim Breitfeller

Please watch this video, it may save you or a love one.

Spread the word!!!!

Happy Cinco De Mayo

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”

~Charles Darwin~

Take Care,
Jimmy B


Friday, April 29, 2011

New technique extends cancer-fighting cells' potency in melanoma patients

New technique extends cancer-fighting cells' potency in melanoma patients

Where did you read this before? Right here!!!! The was a post called A

"Under normal conditions, the reinjected T cells die off in a matter of days. Doctors can increase their staying power by depleting patients' blood of certain regulatory T cells that dampen the anti-tumor T cells' response to cancer or using Interleukin 2, which spurs the growth of T cells.

We are getting so very close to a cure/stabilzation of this diease.

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”

~Charles Darwin~

Take Care,

Jimmy B


Thursday, April 28, 2011

IL-2 Controls the Stability of Foxp3 Expression in TGF-β–Induced Foxp3+ T Cells In Vivo

IL-2 Controls the Stability of Foxp3 Expression in TGF-β–Induced Foxp3+ T Cells In Vivo

Stimulation of naive CD4+Foxp3− T cells in the presence of TGF-β results in the induction of Foxp3 expression and T suppressor function. However, Foxp3 expression in these induced regulatory T cells (iTreg) is unstable, raising the possibility that iTreg would not be useful for treatment of autoimmune diseases. However, When IL-2 is added, the Foxp3 expression is stabilized.

Why is this important, because the tumors secrete the TGF-β and the activated CD4+ T cells secrete the IL-2 for the propagation of the CD4+ T cells. This is the perfect storm for the tumor. The proliferation and survival the of the Tregs, makes it almost immposible to infiltrate the tumors’s microenviroment.

The Tregs compete for the screted IL-2. Depending on the location and how close the CD4+ T cell to the Tregs, The tregs can gain the upper hand by creating a IL-2 sink.

The Tregs must be neutralized to eliminate the surpressiveness that leads to tolarence of the immune system.

Neutralization of IL-2 or disruption of its signaling by deletion of Stat5 diminished the level of Foxp3 expression resulting in decreased suppressor function of the iTreg in vivo.

Blockade or depleting of the Tregs may be the only way to break the tolarence of the immune system.

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”

~Charles Darwin~
Take Care,
Jimmy B

Sunday, April 3, 2011

Understanding cancer immunotherapy..Melanoma ..Jim Breitfeller

Understanding cancer immunotherapy

The basic premise of cancer immunotherapy involves enhancing the body’s own immune system to fight off cancer. It sounds logical and simple in concept, but the practice is complicated.

THE need for more effective and targeted therapy for cancer has always been in the minds of researchers and doctors who treat cancer. The traditional methods of treating cancer, ie surgery, radiation, and chemotherapy, have obvious limitations. Surgery would not be effective in disseminated or widespread diseases, while radiation and chemotherapy cause “collateral damage” due to effects on normal cells while killing off cancer cells. Certainly, a treatment modality utilising and enhancing our immune system to prevent or fight off cancer is a sound and attractive concept, hence the basic premise of cancer immunotherapy (CI).

The traditional methods of treating cancer, i.e surgery, radiation, and chemotherapy, have obvious limitations, hence the surge in interest in cancer immunotherapy. There is a general belief that failure of “immune surveillance” is a main contributory cause of cancer arising in an individual. There is also evidence that in many cancer patients, the immune system slows down the growth and spread of tumours. This means we need a competent immune system to prevent cancer, and to prevent it from spreading once cancer has started. The basis of CI, ie enhancing the body’s own immune system to fight off cancer, sounds logical and simple in concept. Unfortunately, like most things in life, the real scenario proves to be far more complicated, and the quest for effective cancer immunotherapy has taken a long time. But slowly and surely, we are unraveling the mysteries.

What are the ‘tools’ of CI?

To battle cancer cells with immunotherapy, we can either stimulate our immune system, or transfer antibodies or T cells from an outside source. Certainly, immunotherapy involving certain cytokines and antibodies has now become part of standard cancer treatment. Other examples of immunotherapy, especially those involving cellular therapy, remain largely experimental. Although many clinical trials of new forms of immunotherapy are in progress, an enormous amount of research and clinical trials need to be done before the findings can be widely applied.

What are the different types of CI available now?

The cytokines and monoclonal antibodies used are not called drugs or medication, but are labeled as biological immune response modulators (BIRMs), which include cytokines such as interferons, interleukins, colony-stimulating factors and monoclonal antibodies, plus cancer vaccines. We can further categorise them as below:

I. Immunostimulants

Immunostimulants are non-specific agents that tune-up the body’s immune defences. There have been some success with interleukin-2 (IL-2), a potent growth factor for T cells, which have been used in kidney and malignant melanoma, while alpha-interferon (IFN) are used for the treatment of chronic myeloid leukaemia and hairy cell leukaemia.

II. Monoclonal antibodies

Monoclonal antibodies are identical because they are produced by one type of immune cell – all clones of a single parent cell. Currently, most of the antibodies used are produced by recombinant DNA technology. The basis of monoclonal therapy is that different tumours have unique tumour antigens on their surfaces, and the identification of such antigens, such as CD20 on lymphoma cells, and the production of anti-CD20 antibody, ie rituximab, enables a targeted hit on the tumours. This will result in selective killing of lymphoma cells. Indeed, the advent of rituximab has changed the landscape of lymphoma treatment, with improvement in response and survival of patients. Similarly, other monoclonal antibodies such as herceptin (breast cancer), bevacizumab (lung cancer), and alemtuzumab (chronic lymphocytic leukaemia) are making waves in cancer treatment.

III. Immunotoxins and radioimmunotherapy

Monoclonal antibodies can be modified for delivery through toxin, radioisotope, cytokine or other active conjugates. Many such conjugates have been tried with some success. Mylotarg was licensed by the US Food and Drug Administration (FDA) for treatment of acute myeloid leukaemia (AML). Myelotarg is a combination of anti-CD33 and calicheamicin (a cytotoxic compound). However, it was recently withdrawn from the market due to potential severe liver damage. Monoclonal antibodies against tumour antigens can also be coupled to radioactive atoms. The goal with these agents is to limit the destructive power of radiation to those cells (cancerous) that have been “tagged” by the attached monoclonal antibody. Zevalin is a monoclonal antibody against the CD20 molecule on B cells (and lymphomas) conjugated to the radioactive isotope yttrium-90 (90Y). The results in treating B cell lymphoma with radioimmunotherapy are encouraging, though the delivery of such an agent is somewhat cumbersome.

IV. CI with T Cells (allografts or autografts of T cells)

T lymphocytes such as cytotoxic T lymphocytes (CTL) are capable of killing target or tumour cells. How to prime them to act appropriately, ie to kill tumour cells and not other normal cells, remains the challenge. The main reason why allogeneic bone marrow transplants (allografts) work is because of the the post transplant continual attacks on the tumour cells by T cells (graft versus tumour effect) seen in many patients. However the accompanying graft versus host reaction can be severe enough to result in significant mortality and morbidity to the transplant recipient. The same effect of such immunological attacks on tumour cells can be harnessed by donor lymphocyte infusion. This is a double edged sword and needs to be used with extreme caution. Infusion of own or autologous T cells or genetically modified T cells have been attempted with limited success.

V. Cancer vaccines

The response of the patient’s own immune system – immune surveillance – has clearly failed in cancer patients. The purpose of cancer vaccines is to elicit a more powerful active immunity in the patient. Several approaches are being explored. The name “cancer vaccines” is somewhat misleading, as these vaccines are developed to cure cancer and not to prevent it. Dendritic cells (DC) are the most potent antigen-presenting cells. They engulf antigens, process them into peptides, and “present” them to T cells. The making of the vaccine entails, firstly, harvesting DC from patients and exposing them to tumour specific antigens. By injecting the “stimulated” DC back to the body, they may be able to elicit a strong immune response and attack the tumour, utilising the stimulated cytotoxic T lymphocytes. On April 29, 2010, the FDA approved the first anti-cancer vaccine, a patient-specific dendritic cell vaccine for use against advanced prostate cancer. Tumour-antigen specific vaccines are used to immunise the patient with an antigen universally expressed by tumours of that type (but not by normal cells), mixed with some form of adjuvant that will enhance the response. Unlike patient-specific vaccines, these vaccines can be mass-produced for use in anyone with the appropriate tumour.

What are the strengths of immunotherapy?

The most appealling point of CI is that potentially, this is a targeted therapy, and hence the side effects to normal cells would be considerably less. Some chronic myeloid leukaemia patients with relapsed disease post-bone marrow transplant managed to attain long term survival after donor lymphocyte infusion. CI is a very powerful tool indeed, if only we know how to apply it optimally, but we are still grappling how best to titrate the graft versus leukaemia response. Because the side effects are different from conventional chemotherapy, the combination of cytotoxics and immunotherapeutic agents such as rituximab has improved the outcome in lymphoma patients without additional side effects. Because of the favourable safety profile, CI can be given in repeated courses, unlike cytotoxics, which are limited by their cumulative toxicities.

What are the weaknesses or problems of immunotherapy?

The main problem is likely to be the need for time for the immune system to respond to CI, and in some patients with cancer which behaves like a runaway train, eg Burkitt’s lymphoma, time is what the patients do not have. CI is unlikely to work in a large volume tumour, and the tumour needs to be debulked (reduced in size) before CI has a chance to work. CI is costly, and the price is not likely to go down in the near future. Monoclonal antibodies are fabulously expensive. This is even so for a personalised vaccine. For patients who have financial constraints, money is not everything – it is the only thing! Hence, it is likely that such treatment may not be available to those who need it, unless some assistance programme is forthcoming. It is unlikely that CI alone can cure a cancer in the setting of cancer patients whose immune systems have failed them in the first place. We need to learn and strategise how to put different treatment modalities, ie chemotherapy, CI, radiotherapy, in a winning treatment combination. The answer can only come with more painstaking research and careful clinical trials.

Is immunotherapy devoid of side effects?

A resounding NO. Any form of treatment can potentially give rise to side effects. Even taking paracetamol can cause severe allergic reactions, although rarely. Rituximab commonly gives rise to infusion reactions, which are manageable. In 2006, in one of the phase 1 trials of a T cell stimulatory monoclonal antibody called TGN1412 in England, all six of the volunteers were nearly killed, and ended up with multiple organ damage due to unrestrained generalised T cell stimulation. So forget about the no side effects talk. I believe the side effects of immunotherapy are different from conventional treatment like chemotherapy, and we have to learn about them (both short term and long term), and deal with them accordingly. For instance, we now know that the use of chemo-immunotherapy in treating non-Hodgkin’s lymphoma can cause potentially fatal hepatitis B virus activation. This problem is prevented by concurrent antiviral therapy. How does CI fit into a patient’s treatment plan? Can a patient ask for immunotherapy first before following established treatment or can CI be the sole form of treatment? I feel the best person to answer the question is the oncologist/haematologist who is looking after the patient. CI with monoclonal antibodies can be used in induction (initial treatment) or to consolidate the treatment, and in some instances, to remove any minimal residual disease. Cell-based immunotherapy remains experimental and is likely to be offered in a setting of clinical trials. Very rarely is CI used as the sole form of therapy. I honestly feel that clinicians should make the decision. Using inappropriate therapy results in loss of valuable time in tackling the cancer, not to mention the accompanying financial toxicity!

What are the basic questions to ask when one checks out immunotherapy?

The patient really needs to know what he or she is in for. Is the centre a reputable one, and is the treatment approved by authorities such as the FDA or EU (European Union)? Is the treatment potentially curative or merely palliative? Are there other treatment options which may work just as well? What does the procedure entail and what are the potential side effects? The patient, together with the attending doctor, should weigh the benefit versus risk equation, and also the cost effectiveness of the planned treatment. In other words, one should go into any treatment only with eyes widely open. When a treatment sounds too good to be true, it usually is.

Is CI ready for prime time?

It is important to keep our feet firmly on the ground and not be taken by sales propaganda. In some forms of CI, such as monoclonal antibodies treatment, many lives are prolonged and saved, and monoclonal antibodies is now an established treatment modality. We need to tread far more carefully in cell based therapy. To date, the FDA has only approved one, and only one, cancer treatment vaccine, i.e. Provenge (sipuleucel-T). The vaccine is designed for men with advanced prostate cancer who have limited treatment options. Patients will have immune cells purified from their blood, and then combined with a specific protein (an antigen) that stimulates the immune cells to recognise and kill prostate cancer cells. The custom created vaccine is given intravenously in three doses, two weeks apart. Potential reactions include fever and flu-like symptoms. Before we get carried away, the new treatment resulted in a very modest 4.1 month improvement in median survival compared to the placebo group.

Why the surge in interest in CI?

According to the American Cancer Society, immunotherapy, especially cancer vaccines, is still a small field which hasn’t yet proven itself to be better than other types of cancer treatments. However, it’s one that researchers say holds a lot of promise and “many future advances against cancer will probably come from this field”. Interestingly, Time magazine voted in two cancer researchers, Dr Larry Kwak and Dr Doug Schwartzentruber, for its 2010 list of 100 most influential people in the world. Both of them are in the forefront of cancer vaccine research. Dr Kwak is involved in BiovaxID patient-specific vaccine for follicular lymphoma while Dr Schwartzentruber is researching a melanoma vaccine. Both vaccines had good phase 3 trial results and may make their way to bedside use soon. Is there a need for regulation of CI in Malaysia? The answer has to be yes. Unfortunately, we have no shortage of entrepreneurs, and for new therapies, whether it’s stem cell based or cell based, medical supervision is necessary to protect our patients. We don’t want to make news for the wrong reasons. At the end of the day, we should heed Hippocrates’ wise words – to cure sometimes, to comfort always, and not to cause any harm to our patients. This article is contributed by The Star Health & Ageing Panel, which comprises a group of panellists who are not just opinion leaders in their respective fields of medical expertise, but have wide experience in medical health education for the public.

The members of the panel include:

Datuk Prof Dr Tan Hui Meng, consultant urologist; Dr Yap Piang Kian, consultant endocrinologist; Datuk Dr Azhari Rosman, consultant cardiologist; A/Prof Dr Philip Poi, consultant geriatrician; Dr Hew Fen Lee, consultant endocrinologist; Prof Dr Low Wah Yun, psychologist; Datuk Dr Nor Ashikin Mokhtar, consultant obstetrician and gynaecologist; Dr Lee Moon Keen, consultant neurologist; Dr Ting Hoon Chin, consultant dermatologist; Prof Khoo Ee Ming, primary care physician; Dr Ng Soo Chin, consultant haematologist.

For more information, e-mail The Star Health & Ageing Advisory Panel provides this information for educational and communication purposes only and it should not be construed as personal medical advice. Information published in this article is not intended to replace, supplant or augment a consultation with a health professional regarding the reader’s own medical care. The Star Health & Ageing Advisory Panel disclaims any and all liability for injury or other damages that could result from use of the information obtained from this article.


“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”

~Charles Darwin~

Take Care,
Jimmy B


Greetings to One and All

This Blog is dedicated My Brother Kenny B. who passed away in the late 1970's with Cancer before the Internet.

It was he, who showed me How to live and give back. He was wise beyond his years.

Kenny B

Jimmy and Dee

Carepage: Jimmybreitfeller
Jimmy Breitfeller

My Profile as of 2009

My photo
Last July (2005)I was riding my bicycle to work at the Eastman Kodak Research Labs about 3 miles from home. I was wearing a knapsack to carry my things to and from the labs. I started noticing an ache on my back. So I decide to go to the dermatologist. To make the long story short, it was cancer. I knew from my research that I would be needing adjuvant therapy. So I started communicating with Sloan Kettering, University of Pittsburgh Cancer Center, and a couple of others including the Wilmot Cancer Center at Strong. I realized that by telling my story, I might help someone else out there in a similar situation. So to all who are linked by diagnosis or by relation to someone with melanoma, I wish you well. Stay positive, read as much as you can (information helps to eliminate the fear associated with the unknown), and live for today, as no one can predict what tomorrow may bring. Jimmy B. posted 12/15/08


The information contained within this Blog is not meant to replace the examination or advice of your Oncologist or Medical Team. The educational material that is covered here or Linked to, does not cover every detail of each disorder discussed.

Only your physician/Oncologist can make medical decisions and treatment plans that are appropriate for you. But, An Educated Consumer is a Smart consumer.

As Dr. Casey Culberson Said:

"The BEST melanoma patient is an ACTIVE PARTICIPANT in his or her treatment

Melanoma and the “Magic Bullet” (Monoclonal Antibodies)

Just to let you know I posted the first draft of the Melanoma and the “Magic Bullet” (Monoclonal Antibodies). on Melanoma Missionary In the Shared File Section. you can download it for 19.95 (Only kidding) it is Free for the taking.

It is 33 pages long and may help you in your quest for the Yellow Brick Broad. Just to let you know it is only the first draft. Revisions are sure to come. I wanted to get it to the people that need it the most, the Melanoma Patients.


So, where does Interluekin-2 (IL-2) come into play? According to Byung-Scok et al and recent reports, IL-2 is not needed for developmental CD4+ CD25+ Treg cells in the thymus but does play an important role in the maintenance and function in the peripheral.18 Peripheral is defines as secondary system outside the bone marrow and thymus. It entails the site of antigen, immune system interaction. IL-2 is required for the peripheral generation of Tregs based Abbas’s and colleagues research.19

IL-2 prevents the spontaneous apoptosis of the CD4+ CD25+ Treg cells. It has been reported that patients with multiple advance-stage tumors have elevated levels of Tregs within the tumor microenviroment.20 Interluekin-2 is the survival factor for CD4+ CD25+ Treg cells.21 If the addition of IL-2 is on or before the maximum propagation of the CD4+ T cells, the Tregs population can increase 5-fold in a 96 hour period based on certain growth mediums.

By controlling the addition of the endogenous IL-2, one has a knob to turn and can lead to the control of the expansion of the Tregs. When you combined this control with the anti-CTLA-4 blockage, you can shift the balance of the immune response.

Now here is the catch. The maintenance and function of the CD8+ T-cells require CD4+ cells which secrete IL-2. So we don’t want to deplete the CD4+ cells, we want to control the expansion of the Tregs which are a subset of the CD4+ cells. It has been postulated by some researchers that the Anti-CTLA-4 blockage also suppresses the Treg function in a different mechanism. By using IL-2 as the rate limiting factor, we can suppress the CD4+ CD25+ Treg cell expansion by controlling the concentration and timing of the Inerluekin-2 at the tumor microenvironment.

The Interluekin-2 plays another role in this Melanoma Maze. In a study by Janas et al, Il-2 increases the expressions of the perforin and granzyme A, B and C genes in the CD8+ T-cells. This increase expression causes the CD8+ T-cells to mature into Cytoxic T Lymphocytes (CTLs). The exogenous IL-2 is required for the granzyme proteins. As stated previously, CTLs have cytoplasmic granules that contain the proteins perforin and granzymes. A dozen or more perforin molecules insert themselves into the plasma membrane of target cells forming a pore that enables granzymes to enter the cell. Once in the tumor cell, these enzymes are able to breakup (lyse) the cell and destroy it. This is the beginning of the end for the cancer cells. The tumors begin to shrink and the rest is history,

On the other hand, prolong therapy with Il-2 can result in causing apoptotic death of the tumor- specific CD8+ T-cells.23

Clearly in a clinical setting, timing, dose, and exposure to these drugs play a major roll in the immunotherapy, and can have dramatic effects on the outcome.

All it takes is that one magic bullet to start the immune reaction..

Melanoma And The Magic Bullet (Monoclonal Antibodies)

Public Service Announcement

A call for Melanoma Patients by Dr. Steven A Rosenberg

"We continue to see a high rate of clinical responses in our cell transfer immunotherapy treatments for patients with metastatic melanoma", Dr. Rosenberg said.

"We are actively seeking patients for these trials and any note of that on a patient-directed web site would be appreciated."

If you would like to apply for his trials, here is the website and information.

Dr. Rosenberg's information

Dr. Rosenberg's Clinical Trials

For the Warriors

The Melanoma Research Alliance has partnered with Bruce Springsteen, the E Street Band, and the Federici family to alleviate suffering and death from melanoma. Please view Bruce Springsteen’s public service announcement inspired by Danny Federici. Danny was the E Street Band’s organist and keyboard player. He died on April 17, 2008 at Memorial Sloan-Kettering Cancer Center in New York City after a three year battle with melanoma.

Source Fastcures blog

Join the Relay for Life!!!


Dear Family and Friends,

I’ve decided to take a stand and fight back against cancer by participating in the American Cancer Society Relay For Life® event right here in my community! Please support me in this important cause by making a secure, tax-deductible donation online using the link below.

To donate on line now, click here to visit my personal page.
Jimmy B AKA Melanoma_Missionary

Relay For Life® is a life-changing event that brings together more than 3.5 million people worldwide to:

CELEBRATE the lives of those who have battled cancer. The strength of survivors inspires others to continue to fight.

REMEMBER loved ones lost to the disease. At Relay, people who have walked alongside people battling cancer can grieve and find healing.

FIGHT BACK. We Relay because we have been touched by cancer and desperately want to put an end to the disease.

Whatever you can give will help - it all adds up! I greatly appreciate your support and will keep you posted on my progress.

Keep the Fire Burning!!!



Jimmy Breitfeller
Turn off Music before you "Click to Play"
Signs of Melanoma Carcinoma Skin Cancer

How Skin Cancer Develops by " : Dermatology"

Call for Patients with Unresectable Liver Metastases Due to Melanoma

Delcath Systems Granted Orphan-Drug Designations for Cutaneous and Ocular Melanoma

Delcath is actively enrolling patients in a Phase III clinical trial testing its proprietary drug delivery system, known as Percutaneous Hepatic Perfusion (“PHP”), with melphalan for the treatment of ocular and cutaneous melanoma metastatic to the liver.

This NCI-led trial is enrolling patients at leading cancer centers throughout the United States. Commenting on these orphan-drug designations, Richard L. Taney, President and CEO of Delcath, stated, “These favorable designations are important steps in our efforts to secure Delcath’s commercial position upon conclusion of our pivotal Phase III trial for metastatic melanoma. We remain steadfast in our commitment to become the leader in the regional treatment of liver cancers and we continue to enroll patients in this study, and advance our technology and the promise that it offers to patients with these deadly forms of melanoma and other cancers of the liver, all with limited treatment options.”

Orphan drug designation, when granted by the FDA’s Office of Orphan Products Development, allows for up to seven years of market exclusivity upon FDA approval, as well as clinical study incentives, study design assistance, waivers of certain FDA user fees, and potential tax credits.

Current Trial Centers

Phase I Study of Hepatic Arterial Melphalan Infusion and Hepatic Venous Hemofiltration Using
Percutaneously Placed Catheters in Patients With Unresectable Hepatic Malignancies

James F. Pingpank, Jr., MD, FACS
Associate Professor of Surgery
Division of Surgical Oncology
Suite 406, UPMC Cancer Pavillion
5150 Centre Avenue
Pittsburgh, PA 15232
412-692-2852 (Office)
412-692-2520 (Fax)

Blog Archive

Call For Melanoma Patients!!!!

Call For Melanoma Patients!!!!

Dr. Rosenberg Has a New Clinical Trial.

Our latest treatment has a 72% objective response rate with 36% complete responses.

We are currently recruiting patients for our latest trial.

Is there some way to post this “Call for Patients” on the web site?

Steve Rosenberg

Dr. Rosenberg's Clinical Trials

(For a copy of the research paper.. see My Shared files)

The news headlines shown above for Melanoma / Skin Cancer are provided courtesy of Medical News Today.