Saturday, January 10, 2009

Research is Paying off!!!!!! Adoptive Cell Transfer Therapy. Jim Breitfeller

Adoptive Cell transfer Therapy.

I am reading a paper by Dr. Rosenberg on Adoptive Cell transfer Therapy.
See, That was one of my paths that I wanted to go down but I Had the wrong blood type. Mine was HLA-A2 Negative they (Rosenberg) was looking for patients of HLA-A2 positive so I was not a match for the trial. That was on 12/13/05. So I never did the research because I was the wrong type. Well, I am working with another patient that asked me to take a look at this therapy. And Now the pieces are starting to come together.

TIL with a lymphodepleting preparative regimen

"Several methods had been established for the generation of tumor antigen-reactive lymphocyte cultures and evaluated in clinical trials. However, highly cultured, highly expanded cloned lymphocytes lacked potency in vivo. Although bulk TIL could mediate objective clinical responses, they were often of short duration and the bulk TIL were logistically difficult to grow9. Because it had been established that a non-myeloablative conditioning regimen could be safely administered in conjunction with adoptive T-cell transfer and IL-2 in patients with metastatic melanoma, we next evaluated whether highly selected, tumor antigen reactive, bulk TIL populations that were rapidly expanded could mediate anti-tumor responses. In an initial cohort of 13 patients22, our results were markedly different than those seen after administration of cloned lymphocyte cultures. This approach resulted in the persistent repopulation of anti-tumor T cells in the cancer patients, with proliferation of functionally active transferred cells in vivo and traffic to tumor sites. This led to regression of the metastatic melanoma in six of 13 patients as well as the onset of autoimmune melanocyte destruction in some patients.

This initial cohort of patients was followed with accrual of additional patients. We reported the combination of lymphodepleting chemotherapy followed by the adoptive transfer of autologous tumor reactive lymphocytes for the treatment of 35 patients with refractory metastatic melanoma23. All but one of these patients had disease that was refractory to treatment with high-dose IL -2 and 18 had progressive disease after chemotherapy. Patients underwent non-myeloablative lymphodepleting conditioning with cyclophosphamide and fludarabine, followed by cell infusion with autologous tumor-reactive, rapidly expanded TIL cultures and high-dose IL-2 therapy. Eighteen treated patients (51%) experienced objective clinical responses by RECIST criteria, including three complete responses that are ongoing more than three years after treatment. Sites of regression included metastases to lung, liver, lymph nodes, brain, and cutaneous and subcutaneous tissues. Although the toxicities of treatment were acute and severe, including the expected toxicities of high-dose IL-2 therapy and the hematologic suppression of chemotherapy, most toxicities were transient and resolved within two weeks. These results suggested that lymphodepleting chemotherapy followed by the transfer of highly avid anti-tumor lymphocytes could mediate significant tumor regression in heavily pretreated patients with IL-2 refractory metastatic melanoma. Table 2 shows the patients who responded to this treatment, along with the duration of their response as of May, 2007, and the initial sites of disease."

Thank You Dr. Roesenberg!!!!!!!!!!!!!!!!!!

CR= complete response
PR= partial response

Questions that need to be answered:

1)Were they all HLA-A2?

2) what blood type? O, A ab...?

3) What type of Melanoma? ( Nodular,Superficial spreading,Lentigo maligna and Acrallentiginous melanoma


There are four pathologic types of cutaneous melanoma each with a characteristic growth pattern. (1) Superficial spreading melanoma is the most common type, accounting for 70% of all cases. This type typically arises from a pre-existing nevus and expands in a radial fashion before it enters a vertical growth phase. (2) Nodular melanoma, a more aggressive tumor, accounts for approximately 15 to 30% of cases. This lesion arises de novo from normal skin and has no radial growth phase. It is found more commonly in males. (3) Lentigo maligna melanoma accounts for less than 10% of cases. This type of lesion is found more commonly in females and the elderly population. The lesions are typically large and flat, follow an indolent growth course, and rarely metastasize. (4) Acrallentiginous melanoma also accounts for less than 10% of lesions, but occurs in a higher proportion (35 to 60%) of nonwhite patients.


Genetically alters some cells and reintroduces them to stimilate the T cell, to create Signal # 1 and the IL-2 is there to do the cell to cell communication (signal #2)

Uses CTLA-4 Blockage to stimulate the T Cell to create signal # 1 and the IL-2 is there to do the cell to cell communication (signal #2)

This first interaction involves the CD4 or CD8 proteins which form a complex with the CD3 protein to bind to the MHC molecule of the (APC). Antigen-presenting cell This is also called "Signal 1" and its main purpose is T cell activation.

However, this is insufficient for producing a T cell response by itself.

In fact, lack of further stimulatory signals sends the T cell into anergy. Anergy is a term in immunobiology that describes a lack of reaction by the body's defense mechanisms to foreign substances.

The Second costimulatory signal necessary to continue the immune response can come from B7-CD28 and CD40-CD40L interactions. The primary role of the B7 proteins is to give a second signal to the T cell.

The B7 protein/receptor is present on the Antigen-presenting cell and is able to interact with the CD28 receptor on the T cell surface; this is also known as "Signal 2". There are other activation signals which play a role in immune responses.

On these T cells there is are family receptors whose job is downregulate the T cell activation so the immune system maintains metabolic equilibrium so the immune system doesn’t start an autoimmune response and cause it to attack itself. One of these receptors is Cytotoxic T lymphocyte-associated antigen (CTLA4).

It was also shown that the anti-CTLA-4 antibodies had a greater affinity to CTLA-4 than the B7 receptor. So by doing the CTLA-4 Therapy, it allowed signal 1 to become active.

So in the presents of the CTLA-4 antibody Therapy, I my case, we may have extended the antitumor response of the T-cells. This left Signal 1 active.

We then, hit the immune system with High dose of IL-2. This must have stimulated the cell to cell communication (Signal 2) causing the immune response to kick in against the foreign molecule (The Tumor)

It is important to know your Blood Chemistry!!!!!!!!!!!!!

Your blood chemistry will lead you down the right path!!!!!!!!!!!!!!!

I also believe that we need to be carefull on how the protcol is set up.

I have read that the combo CTLA-4 and the IL-2 had the same response as the IL-2 alone.

I think it is because they were flooding the # 2 signal cell to cell) and drowning out the T cell Activation. It is like two wave fuctions coming together. If they are in perfect harmony, they will build off of each other and double. If they come at each other at the other 180, the wave will be cancelled out. Something like Sonar.

This just my Hypothesis.

They is probably alot more Biochemistry going on than how I explained it.

But I am not a Biochemist.

Jimmy B


  1. Great site! Thanks for all the information!

    Fellow Melanoma Warrior
    Kerri Pierce
    Stage IIIa
    NED 6/29/07

  2. Kerri, Thanks for posting!!!!

    I thought I was talking to myself!!!!!

    I am here to help, there is way to much info on the net.


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.