Melanoma_Missionary: August 2011

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 kDa.in 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

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Disclaimer

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
(not a PASSIVE RECIPIENT)"

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.

Preview:

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..

https://app.box.com/shared/kjgr6dkztj

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

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.

http://www.melanomaresearchalliance.org/news/PSA/

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!!!

Sincerely,

Jimmy Breitfeller

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)
PingpankJF@UPMC.edu

Melanoma_Missionary

Friday, August 26, 2011

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

Tuesday, August 9, 2011

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

Greetings to One and All

My Profile as of 2009

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Melanoma and the “Magic Bullet” (Monoclonal Antibodies)

Public Service Announcement

Join the Relay for Life!!!

How Skin Cancer Develops by "About.com : Dermatology"

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Call For Melanoma Patients!!!!

List of Companies that are Helping the Melanoma Cause