As I Continue my Quest, I have come to another Windmill..Melanoma..Jim Breitfeller

As I Continue my Quest, I have come to another Windmill.

Anti-CTLA-4 Blockage maybe coming back to compassionate care or better yet,may be getting ready to seek FDA approval.

I have stumble upon another Review Article by Dr. Kim Margolin from 2008.

"Moving forward with immunotherapy: the rationale for anti-CTLA-4 therapy in melanoma."

Source:http://www.communityoncology.net/journal/articles/0507367.pdf
Moving forward with immunotherapy: the rationale for anti-CTLA-4 therapy in melanoma

If you look closely at the tables, you know why Brisol-Meyer Squibb aquired Medarex for their "String of Pearls".

This is the quote I like the Best:

"The preliminary results of these trials are encouraging, considering most patients were previously treated for advanced melanoma. The possibility that anti-CTLA-4 antibodies, used as single agents, will be superior to proven therapies, ie, dacarbazine or IL-2, will be tested in phase III trials. Of greater promise may be the combination of these agents in carefully timed sequence with cytotoxic or other immunotherapeutic strategies."

See , I believe that the combination therapies Hold the greatest Promise.
I can vouch for that. NED FOR OVER 25 MONTHS AND STILL COUNTING!!!!!

Please seek out this therapy if you need it. It could extend or even save your life.



Take Care,

Jimmy B

Woman Diagnosed with Advanced Melanoma in 2005 Remains Disease-Free..Melanoma..Jim Breitfeller

Woman Diagnosed with Advanced Melanoma in 2005 Remains Disease-Free

Woman Diagnosed with Advanced Melanoma in 2005 Remains Disease-Free Thanks to Clinical Trial Conducted at St. Luke’s

Cancer Expert Lee B. Riley, MD, PhD Served as Co-Investigator and Co-Author in the Phase III Melanoma Vaccine Trial for Patients with Advanced Disease

Suzanne Lapierre-Roman of Allentown was diagnosed with metastatic melanoma at age 29 in July of 2005. The news came as a complete surprise. While pregnant with her fourth child, Suzanne was experiencing pain thought to be caused by her gallbladder, and soon after delivery, had it removed. Test results that came back showed she had cancer – advanced melanoma. “It was a shock,” she says. “At the time, I didn’t even know what melanoma was.”

Suzanne was first seen at a number of university hospitals in Philadelphia and then a local hospital. “I wasn’t given much hope,” she says. “I was told to go on chemotherapy. Then, I heard about Dr. Lee Riley at St. Luke’s. He tested me to see if I would qualify for a melanoma clinical trial. I went on in October 2005.”

The treatment, formulated by National Cancer Institute (NCI) investigators, involves the use of a potent designer peptide vaccine gp100:209-217 (210M) which mimics the antigen that sits on the surface of a patient’s own tumor cells. On its own, the peptide shows little activity. However, in this trial, the vaccine was given in combination with the FDA-approved inpatient therapy for melanoma, High-Dose IL-2, made from a natural protein produced by the body.Dr. Riley, Medical Director of St. Luke’s Cancer Center, served as a co-author and a clinical investigator for the randomized study. St. Luke’s Cancer Center in Bethlehem was the only site in Pennsylvania to participate in the trial and was a major contributor of study participants, including Suzanne. Dr. Riley joined on as an investigator in the study in 2002. The promising results of the trial were presented at the June 2009 meeting of the American Society of Clinical Oncology in Orlando, Florida.

It’s been nearly four years since Suzanne went on the trial and today she is totally disease-free. “Dr. Riley was the only one who gave me hope,” she says. “He told me, ‘When this treatment works, it’s a home run.’ Well, I got my home run. Today, I don’t have any signs of the disease. Dr. Riley is just awesome; I owe him my life.”

“Suzanne’s great results are typical for someone who responds to IL-2, and there is a very good chance she will not have a recurrence. This study suggests that, in the future, more than twice as many people should respond the way Suzanne has,” says Dr. Riley.

Dr. Riley stresses the significance of this study. “The trial has demonstrated for the first time that, a vaccine can improve the outcome of patients with the most advanced stage of melanoma (stage IV). This is a major advance for cancer vaccine research and should stimulate additional cancer vaccine studies.”

More about the study

One hundred and eighty-five patients were enrolled in the study in 21 states from 2000 to 2007. The majority of patients in this study were between the ages of 31 and 60 and had advanced disease. All of the patients were heavily pretreated with surgery and, in some cases, patients had also undergone prior chemotherapy, radiation therapy, or immunotherapy including IL-2.

Study participants received two to four vaccine injections every three weeks. The study showed that those who received the vaccine with high-dose IL-2 had a significant response rate, 22.1 percent compared to 9.7 percent who just received the high-dose IL-2. The overall survival for those receiving the vaccine with IL-2 was 17.6 months compared to 12.8 months (p=0.084).

“The vaccine induces anti-tumor T-cells and the IL-2 stimulates the T-cells to grow and divide,” says Dr. Riley. “T-cells belong to a group of white blood cells known as lymphocytes and play a central role in cell-mediated immunity.”

Now that the study is over, the trial’s investigators are evaluating ways to move it forward so that others with advanced melanoma may also benefit.

Source:http://wellspringhealthandstyle.com/2009/08/20/woman-diagnosed-with-advanced-melanoma-in-2005-remains-disease-free/

The use of a potent designer peptide vaccine gp100:209-217 (210M) which mimics the antigen that sits on the surface of a patient’s own tumor cells. It is used as the Antigen, for the Antigen Presenting Cell (APC)





Take Care,

Jimmy B

Bristol's Cancer Bet!!! Melanoma ..Jim Breitfeller

Bristol's Cancer Bet

Robert Langreth, 07.23.09, 05:26 PM EDT
Cancer immunotherapy has mostly been a failure so far. With its $2.4B purchase of Medarex, the company wagers it has found a winner.

Bristol's Cancer Bet


Attempts to spur the immune system to kill tumors have mostly failed in trials. Now Bristol-Myers Squibb is betting billions that it can make immune-targeting therapies finally work against cancer.

Its $2.4 billion cash acquisition of the biotech firm Medarex ( MEDX - news - people ), announced late Wednesday, represents a giant gamble that immunotherapy will become the next big thing in cancer treatment. Medarex's lead drug, ipilimumab, now in a final-stage trial for advanced melanoma, doesn't target tumors directly at all. Instead it works by removing the brakes on the immune system so it can attack and kill the tumor.


Yahoo! BuzzIn recent years, evidence has built that the immune system can sometimes attack and kill cancer cells--sometimes--but that cancer finds ways to fight back and evade or blunt the attack. (See "Cancer Miracles") For some people with advanced cancer, ipilimumab may be just enough to trigger a full-fledged anti-tumor attack. Bristol-Myers Squibb ( BMY - news - people ) has been collaborating with Medarex for years but now will get full rights to the drug.

"We wouldn't be betting $2.4 billion in cash unless we were optimistic" it would work, said Bristol-Myers Chief Executive James Cornelius in a conference call. "This will not be a cure-all for all types of cancer" but it could be "complementary to therapies that are out there today." Medarex has other cancer immunotherapies in earlier stages of testing, as well as drugs targeting lupus, rheumatoid arthritis and inflammatory bowel disease.

Bristol's buy is a risky move because numerous treatments and vaccines that aim to stimulate the body against cancer have mostly failed. One of the few that has worked so far is an experimental prostate cancer vaccine from Dendreon ( DNDN - news - people ) that recently had good trial results. The immune system is one of the more complicated parts of the body and doctors are only beginning to understand its intricacies. Another immune-boosting therapy against cancer, the natural immune system protein interleukin-2, has been limited by severe side effects.

Most trials of ipilimumab to date have been in advanced melanoma, where a small percentage of patients have experienced spectacular long-lasting remissions, even as the drug appears to do relatively little for the majority. Why more patients don't respond is a subject of intense research at laboratories worldwide. Some patients get autoimmune side-effects.

My Comment:

They will only get Synergistic complete responses when they use ipilimumab in combination with IL-2. You also will have to have the right antigen to be presented.Timing when the drugs are introduced in the therapy plays a critical roll in the outcome of the immune response.






Take Care,

Jimmy B

Characterization of the Cytolytic Activity of CD4+ and CD8+ Tumor-infiltrating Lymphocytes in Human Renal Cell Carcinoma..Melanoma ..Jim Breitfeller

Characterization of the Cytolytic Activity of CD4+ and CD8+ Tumor-infiltrating Lymphocytes in Human Renal Cell Carcinoma

This paper is the one of the last papers to be incorporated into my Masterpiece called "Melanoma and the Majic Bullet (Monoclonal antibodies)"

I am going to be scarce for a while so I can finnish the paper for Us.
Some of you have gotten to see bits and pieces of it as I have been posting this last year. I believe it will turn heads. "Always think ouside of the box"

Characterization of the Cytolytic Activity of CD4+ and CD8+ Tumor-infiltrating Lymphocytes in Human Renal Cell Carcinoma


If it gets too hard to read, just look at the two graphs on page 2366. One graph is for the growth curve CD4+ T cells and the other is the CD8+ T cells. Check out the time line and then go back through my posts and you will find simular growth curve data base on my and Dr. Itoh's paper. So the growth curves are repeatable which makes my theory even stronger.

As I will say it again, "It is all in the timing of the Addition of the IL-2"


Take Care,

Jimmy B

Peptide Vaccine Significantly Improves Response in Metastatic Melanoma, but also Rasies questions.Melanoma..Jim Breitfeller

Peptide Vaccine Significantly Improves Response in Metastatic Melanoma, but also Rasies questions.

The current study raises several questions, Dr. Ribas said, including the following:
Question- How does high-dose IL-2 induce tumor regression? "With over 20 years of study, we still don't have an answer."

Answer_I have a theory: The NaiveCD4 + the helper T cell, when activated, the Helper T –cell secretes mostly IL-2 which promotes growth and proliferation, and activation of T-cells, helper T cells and Natural Killer Cells. Once the helper cells mulitply, they start secreting other cytokines base on their costimulatory signals., concentration of antigen, and exposure to their microenviroment. This attracts more immune cells and the assault on the foreign invader begins. The HD IL-2 helps activates the CD4-T cell.Cell to to cell comunication.

At the Lymp Node drainage area, the lymphocytes (CD4+ and CD8+) with their T-cell receptors (TCRs) are able to scan the Dendtric cells (DC’s) for antigen-MHC molecules. (ag-MHC) major histocompatability complex (class I or II). Based on the two signal model, a second signal from CD28 molecule is needed to activate the T-cells (T-lymphocytes). If communcation breaksdown, and the TCR signal only happens, it can lead to tolerance by means of fuctional paralysis of the (APCs) Antigen presenting cells (Anergy) or by the induction of clonal deletion (apoptosis).

Anergic cells can act as regulatory T cells by competing at the sites of antigen presentation and adsorbing out stimulatory cytokines such as IL-2. This can halt the activation of the T- lymphocytes and no immune response is initiated. But after activation of the CD4+ T cells and growth of the T- cells, they cross-prime the CD8+ T cells and in the presence of HD IL-2 mature into (CTL) Cytotoxic T lymphocytes. Cross-priming is another name for cross-presentation. The role of the CD8+ T cells is to monitor all the cells of the body, ready to destroy any that express foreign antigen fragments in their class I molecules.

CTLs have cytoplasmic granules that contain the proteins perforin and granzymes. When the CTL binds to its target, the contents of the granules are discharged. 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. Granzymes are serine proteases. The serine proteases are a family of enzymes that cut certain bonds in other proteins. It is similar to what is in your laundry detergent. They are known as detergent enzymes. They break the bond between the dirt and the fabric. By breaking up these proteins, they start destroying the intracellular workings of the tumor cells.

Question- How do gp100 peptides improve outcomes of high-dose IL-2?


Answer-My guess, They attach to the Antigenic protein and form some sort of a complex and when the complex is processed by the Antigen Presenting Cell you now have more antigenic fragments then you would other wise, which means activating more T-cells improving the microenvironment.






The answers are base on my research and intuition.



Take Care,

Jimmy B