Thursday, August 26, 2010

Promising new Melanoma Drug, PLX4032: Questions and Answers

Promising new melanoma drug: Questions and answers

By Liz Szabo, USA TODAY

A new drug for the treatment of advanced melanoma is generating rare excitement and optimism among cancer doctors. USA TODAYasked experts to explain the drug's benefits and limitations.
Q: Why is the drug promising?

A: The drug, PLX4032, shrank tumors in 26 of 32 melanoma patients who had a key mutation in their tumors, according to a study in today's New England Journal of Medicine.

That's "remarkable," because patients in small, early trials such as this often get no benefit at all. Typically, experimental drugs shrink tumors in only 5% to 10% of patients, says Keiran Smalley of the Moffitt Cancer Center and Research Institute in Tampa, who wasn't involved in the study.

Some patients began showing improvement within only a few days, says Lynn Schuchter of the University of Pennsylvania, who also worked on the study.

Q: Were those patients cured?

A: In two patients, tumors disappeared, and some patients' disease remains in check. It's too early to know whether patients will stay in remission, however. The median remission was more than seven months, the study says.

But even shrinking tumors is relatively rare in advanced melanoma that has spread to other organs. The two approved drugs for melanoma — a chemotherapy called dacarbazine and an immune therapy called interleukin-2 — shrink tumors for only about 10% to 20% of patients, the study says.

Q: Does the drug help all patients?

A: No, it helps only the roughly 50% of patients whose tumors have the mutations in a gene called BRAF, the study says. Patients who don't have the mutation get no benefit.

If the drug is approved, doctors probably will begin testing all patients with advanced melanoma for the mutations. A test such as this probably would cost a few hundred dollars, says the study's lead author, Keith Flaherty of Massachusetts General Hospital in Boston.

Q: How is the drug different from other treatments?

A: Unlike conventional chemo, which kills all fast-growing cells, the new drug — also known as RG7204 — is considered a "targeted therapy" because it aims to block a specific mutation found only in certain melanoma cells.

Q: What about side effects?

A: Because PLX4032 leaves most healthy cells alone, it causes far fewer side effects than chemo, Flaherty says. High-dose IL-2, for example, can cause life-threatening side effects and is given only in the hospital, so patients can be closely monitored. Patients can take PLX4032, a pill, at home.

But even relatively mild side effects can become bothersome over time, says Vernon Sondak of the Moffitt Cancer Center and Research Institute in Tampa, who wasn't involved in the study.

If PLX4032 helps keep patients alive a long time — either by itself or when combined with other experimental drugs — patients may be more troubled by fatigue, rash and joint pain, Sondak says.

Q: Who financed the study?

A: The study was paid for by the drug's co-developers, Plexxikon and Roche Pharmaceuticals.

Q: What will it cost?

A: The companies haven't announced a price, because the drug is still in early trials. Flaherty notes, however, that many new cancer therapies cost $5,000 to $7,000 a month.

Q: Is it possible to get the new drug?

A: Yes. Doctors are still enrolling patients with advanced melanoma in a large trial of 680 patients who haven't gotten other treatment. Additional studies are expected to be launched next year, Flaherty says. More information about PLX4032 is available by calling 888-662-6728.

Other experimental drugs for melanoma — including ones very similar to PLX4032 — also are being developed. More information can be found at

Q: When might the drug be approved?

A: If additional studies are positive, Roche Pharmaceuticals plans to apply for FDA approval in 2011, spokeswoman Amy Berry says. In June, PLX4032 was given "fast-track" status by the Food and Drug Administration — a process that helps speed up development of drugs that fill unmet needs.


Since it helps only the roughly 50% of patients whose tumors have the mutations in a gene called BRAF, Ipilimumab,PD-1 and Interluekin-2 would be other therapies to try.

My gut feeling is that we can beat Melanoma with combinatorial Therapy.

We just need to get the Drug companies and the Oncologists on board

“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


The Cancer Trial Bristol and Roche Must Do Now..Melanoma ..Jim Breitfeller

The Cancer Trial Bristol and Roche Must Do Now

Author: Robert Langreth
Aug. 26 2010 - 12:31 pm

Novartis’ Gleevec is an exception. Curing cancer won’t happen with a single drug. Common cancers are too complicated and have too many mutations. The solution, many cancer researchers hope, are smart drug combos that hit multiple tumor weak points at once.

But what happens when two drug companies own the experimental drugs that need to be combined?

The small world of melanoma all of sudden faces this lucky problem. For decades melanoma was a barren wasteland of drug development. Almost nothing worked.

Image via Wikipedia
Now there are two promising new drugs. Ipilimumab from Bristol-Myers Squibb stimulates the immune system against cancer. Based on pioneering research by James Allison, the drug boosted patient survival by three months, a big trial found.

Meanwhile, PLX4032 from Roche and Plexxikon works via a different mechanism and shrinks tumors in a mind-boggling 80% of melanoma patients whose tumors have a mutation called in a gene called BRAF, These results were published this week in the New England Journal of Medicine. But the effects often don’t last long; resistance hits after a matter of months. It has not been proven to extend how long patients live. GlaxoSmithkline is testing a similar drug.

The obvious thing to do: combine the Roche and Bristol drugs in a trial to see if both drugs produce a powerful one-two punch. The logic, points out Memorial Sloan Kettering melanoma expert Paul Chapman, is compelling. Both drugs work by different mechanisms and don’t have obvious overlapping side effects. The Roche braf drug kicks in quickly, which can help symptoms, while the Bristol-Myers drug takes months to act, only occasionally produces big tumor shinkage. But when it does the effects can be almost miraculous.

Dead tissue produced by the anti-tumor effects of the Roche drug, could help stimulate the immune system and enhance the impact of the Bristol drug. In test tube experiments, blocking BRAF protein in melanoma cells appeared to enhance the ability of the immune system’s killer t-cells to recognize melanoma, according to a recent Massachusetts General Hospital study.

The good news, says Massachusetts General Hospital’s Keith Flaherty, is that both Bristol and Roche appear willing to collaborate. Flaherty says that cancer doctors cajoled the two sides to discuss a combo trial at the June ASCO meeting of cancer doctors. “This discussion went better than any of us expected,” he says. Both Roche and Bristol confirmed to Forbes that they are exploring combination therapy.

“Everyone wants to do it. It is a no-brainer,” says Chapman. But the logistics are extremely tricky, he says, and a trial design has not been finalized. Whose drug is the “control therapy” to which the combo is compared? Which company gets the patent on the combo, if there is one? Who gets the blame if the combo produces nasty side effects? “There are a lot of wild cards here, we are working on this, it is going to happen,” says Chapman. Another issue: both companies are naturally focused on getting their drugs approved individually first.

It is heartening that Bristol and Roche are amenable to getting together. Too often, corporate bureaucracy has trumped patient needs. One exception is a dual cancer drug trial that Merck and AstraZeneca announced last year.

Flaherty says that a combination trial won’t begin until April of 2011 at earliest. That is far too long. For melanoma patients’ sake, Bristol and Roche need to begin this trial sooner rather than later.


This combinatorial is another therapy that has a real potential. It combines IFN,DTIC,Anti-CTLA-4 (Ipilimumab) and IL-2. it has worked for a number od Melanoma patientss.

We need to get these drug companies to work together for the common good. There is enough room for all the drug companies to get a piece of the Melanoma Action. One therapy will not work.

Combinatorial therapy is the road to success.


“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, August 22, 2010

Perspectives on the Management of Metastatic Melanoma: The Expanding Role of Immunotherapy..Jim Breitfeller

Perspectives on the Management of Metastatic Melanoma: The Expanding Role of Immunotherapy CME
John M. Kirkwood, MD; Jedd Wolchok, MD, PhD; Vernon K. Sondak, MD


Perspectives on the Management of Metastatic Melanoma: The Expanding Role of Immunotherapy

“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


Treating Cancer by Targeting the Immune System ..Melanoma ..Jim Breitfeller

Treating Cancer by Targeting the Immune System
Editorial by Dr. Patrick Hwu of MD Anderson

"There is currently great interest in the targeted therapy of cancer. Antibodies that target specific antigens on the surface of cancer cells — such as rituximab, which binds to CD20 on lymphoid tumors, and trastuzumab, which blocks HER2 on breast-cancer cells — were early successes.

However, a novel method of using antibodies to stimulate an antitumor response was pioneered in the mid-1990s by James Allison and colleagues.1
Because the body’s immune response, if left unchecked, can result in autoimmunity, we have evolved a number of immune “checkpoints” that
work as braking mechanisms to counterbalance immune activation. Studies in animals have shown that inhibition of these checkpoints — such as
with an antibody against the cytotoxic T-lymphocyte– associated antigen 4 (CTLA-4) molecule, an inhibitory membrane protein that is expressed after T-cell activation — enhances immune activation against cancer cells, resulting in significant antitumor effects."

Source:Treating Cancer by Targeting the Immune System

The Main Take away is:

"Despite dramatic effects in a subgroup of patientsreceiving the anti–CTLA-4 drug, the majority of patients with metastatic melanoma do not
respond to this agent, and further work is vital to improve these results. Future efforts should include the rational combination of anti–CTLA-4 agents or alternative checkpoint inhibitors with targeted therapies or other immune agents. Instead of attempting to marginally increase the median survival, the primary goal of these new combination therapies should be to enhance the percentage of long-term survivors, thereby elevating the “tail” of the survival curve. It should be possible to realize this goal if there is adequate synergy and cooperation among academia, regulatory agencies, and the pharmaceutical industry"

We all need to work together to find the CURE.

Melanoma and the Magic Bullet [Monoclonal Antibodies]

“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


PLX4032 May Clear Path for Individualized Treatment of Metastatic Melanoma..Jim Breitfeller

PLX4032 May Clear Path for Individualized Treatment of Metastatic Melanoma

Elsevier Global Medical News. 2010 Aug 20, MG Sullivan

Chicago -- A drug that targets metastatic melanoma with mutations in the BRAF oncogene may be the first step on a path to individualized chemotherapy for patients with these formerly untreatable cancers.

"We are rapidly unraveling the molecular underpinnings of these tumors, and discovering the mechanisms by which they drive melanoma growth. These insights allow us to develop and select drugs on the basis of every patient's individual genome," Dr. Hensin Tsao said at the American Academy of Dermatology's Academy 2010 meeting.

PLX4032 is the first drug to successfully shrink both cutaneous and internal metastases of BRAF-mutated melanomas, said Dr. Tsao, a dermatologist who is director of the Massachusetts General Hospital Melanoma Genetics Program in Boston. His colleague, Dr. Keith Flaherty, is about to publish data from the drug's phase II trial of 87 patients; 81 percent of those with the BRAF-mutated melanoma responded with a 30 percent or more shrinkage of the targeted lesions.

After a phase I safety and dose-finding trial, investigators settled on an oral dose of 960 mg twice daily for the phase II study. The effect was little short of remarkable, Dr. Flaherty, director of developmental therapeutics at the Massachusetts General Hospital Cancer Center, said in an interview.

"My first responding patient had cutaneous and internal metastases, and the cutaneous metastases were clearly getting better right in front of our eyes," he said. "We have seen this in some other areas of cancer, but never in melanoma, which before this was a clinical scenario with an unmet need for therapy."

PLX4032, first engineered by the Berkeley, Calif., company Plexxikon Inc. and being developed in partnership with Roche, is not a foolproof cure, Dr. Tsao said in an interview. "It's clearly a huge leap forward for the patients who responded so rapidly, yet most are still progressing despite being on the drug. It's the best stun we've ever seen for melanoma, but it's not a permanent kill."

Sustained response in the phase I and II trials has varied from only two months to up to two years, Dr. Flaherty said. He could find no significant predictors of progression or response among the group except for initial tumor number and size. Typically, he said, the patients with the greatest mass of metastatic disease had the shortest duration of response, while those with a smaller tumor burden had a longer duration of response.

"When you have metastatic melanoma, your days are numbered--and numbered in a way we can't predict when metastatic disease is diagnosed," Dr. Flaherty said. "What this therapy does is push out the time until the disease worsens. We are not yet smart enough to understand what it is that allows a tumor to work its way around the drug's activity."

Chemotherapy-resistant cancers are nothing new, Dr. Tsao noted. What will be new is the full investigation of melanoma's genetic pathways, and the development of drugs to block them in multiple ways. "The next frontier will be to understand all the ways that melanoma can outsmart treatment. We may have to use multiple therapies to corner it. So a full discovery of all melanoma's potential vulnerabilities is very important."


The quote of the day

"The next frontier will be to understand all the ways that melanoma can outsmart treatment. We may have to use multiple therapies to corner it. So a full discovery of all melanoma's potential vulnerabilities is very important."

~Dr. Flaherty~

“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


Is a Cure in Sight?Melanoma..Jim Breitfeller

-Melanoma Researchers Striving for New Therapies for Patients-
HILLSBOROUGH, N.J.—The recent debut of “The Big C” on Showtime has placed some of Hollywood’s spotlight on melanoma, the deadliest form of skin cancer. The show features award-winning actress Laura Linney as Cathy Jamison, a middle-aged woman who receives a diagnosis of stage IV melanoma, and the storyline follows her pursuit to enjoy life and find peace in her diagnosis.

Yet “The Big C” bypasses one of the key issues that people with melanoma face – the difficulties in navigating the limited choices in treatment. Linney’s character chooses no treatment, in contrast to the majority of melanoma patients who work tirelessly to find the best therapeutic option for themselves.

In recent years, new drugs have shown promise and these advances give people with melanoma reason to seek out care. “We strongly believe that, unlike Linney’s character, those who have been diagnosed should consider the full range of options that are available to them in fighting melanoma, from surgery to approved treatments and promising clinical trials,” said Tim Turnham, executive director of the Melanoma Research Foundation (MRF).

Progress in expanding options for those with advanced melanoma has received significant media coverage recently, particularly news from the annual meeting of the American Society of Clinical Oncology (ASCO) held in June. A new study was presented that found promising results for those diagnosed with metastatic melanoma, and showed an improved overall survival for the first time in 30 years. There has not been a new drug approved for those with advanced melanoma in over a decade.

Increasingly, scientists and researchers suspect that there is no single drug that will effectively treat melanoma and believe that a combination or “cocktail” of drugs may be the answer to treating advanced melanoma. However, it can be difficult to coordinate clinical trials for drugs.

Is a Cure in Sight?

Melanoma and the Magic Bullet [Monoclonal Antibodies]


“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 20, 2010

Diagnosing Skin Cancer Without Biopsy..Melanoma ..Jim Breitfeller

BACKGROUND: Skin cancer is the most common form of cancer, affecting approximately 1 million people annually. The easiest way to recognize skin cancer and the possible formation is a change in skin appearance such as color or soreness. Doctors say if there is a new growth that has appeared and will not go away, this is also a sign of the possible formation of skin cancer. There are three different types of skin cancer: basal cell carcinoma, squamous cell carcinoma, and melanoma. Melanoma is the most serious form of the three.

To diagnose skin cancer, doctors must do a biopsy, or take a sample of the skin and send it to a lab to be processed. It can take more than a week for the patient to get results. According to the American Cancer Society, as many as 80 percent of biopsies for some types of cancers come back negative.

TREATMENT: There are four main types of treatment for people who have skin cancer: surgery (which also includes dermabrasion and laser surgery), radiation therapy, chemotherapy, and photodynamic therapy (which uses a drug and a certain type of laser to kill cancer cells). A new type of treatment, called biological therapy, is being tested in clinical trials. With biological therapy, doctors use the patient's immune system to fight the cancer.

DIAGNOSING SKIN CANCER WITHOUT A BIOPSY: Researchers say they are working on an invention that could radically change how doctors find skin cancer. It is a hand-held, non-invasive cancer scanner that diagnoses skin lesions on a patient. The handheld scanner uses a lens to look at a patient's skin, but instead of illuminating the skin with normal white light, the device uses laser light. The laser light is used to form an image of the skin's cellular structure, and it monitors the way a
patient's cells change the reflected laser light. Doctors say those changes can tell them the chemical composition of the skin cells. Doctors would then compare that chemical signature to a database containing the chemical signatures of known cancers to see whether the patient's cells are cancerous. The device would be able to tell if a patient has a form of skin cancer within minutes.

MelaFind uses a digital camera to record suspect skin patches in 10 different bands of light, including a deep probing infrared beam that examines cells below the skin's surface. The collected images are sent to a computer and compared against thousands of malignant and benign skin images, determining in seconds whether skin cancer is likely and eliminating the need for painful, scarring biopsies.

This pattern-recognition technology was originally developed by the Department of Defense for use in spy satellites to distinguish potential military targets from civilian objects.

In a clinical trial at seven locations across the U.S. last February, researchers used MelaFind to study more than 1,800 skin lesions from 1,300 patients, finding that MelaFind's ability to accurately rule out skin cancer was 2.5 times greater than that of dermatologists.

MelaFind demonstrated 98% sensitivity (correctly identifying the disease when it is actually present) in the detection of melanomas (identifying 125 out of 127 overall melanomas) and 9.5% specificity (ability to rule out the disease when it is not present), compared to 3.6% for the 39 dermatologists who participated in the study.

It is up for review with the FDA and hopfully will get approval by the end od this.

MelaFind is a breakthrough product with the potential to save lives!!!!

“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, August 18, 2010

Researchers develop new cancer vaccine mobilizing immune cells

Researchers develop new cancer vaccine mobilizing immune cells

(Mainichi Japan) August 18, 2010

Japanese researchers have developed a cancer immunotherapy vaccine that mobilizes two types of immune cells at the same time, providing hope for the development of more effective cancer treatment.

The vaccine, developed by researchers including Takashi Nishimura of Hokkaido University, activates immune system cells called killer T cells and helper T cells at the same time, which is said to boost patients' immunity. The researchers confirmed that the vaccine cleared up cancer in a patient for whom anticancer drugs and radiation therapy had proven ineffective.

"We want to conduct more clinical trials and make decisions on its detailed effectiveness. At the same time we want to conduct research on synthesis processes for more effective vaccines," Nishimura said.

Helper T cells are a type of lymphocyte, a kind of white blood cell in the immune system, that help keep track of antigens, including cancer antigens. They aid the action of killer T cells, which attack cancer cells directly.

Previous vaccines focused on the activity of killer T cells alone, but Nishimura and the other researchers set about making both helper and killer T cells active. They created a vaccine dubbed "H/K-HELP" that artificially bound about 40 amino acids that work against cancer from peptides, which are strings of amino acids.

In clinical tests performed at Hokkaido University Hospital and Kinki University Hospital, the researchers administered the vaccine to a breast cancer patient and a patient whose lung cancer had spread to cause bowel cancer. They found that the cancer cleared up or restrained the focus of the cancer.

The researchers plan to announce their findings at a symposium of the International Congress of Immunology beginning in Kobe on Aug. 22.


We are getting closer!!!!!!CURE!!!!!!

“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

Understanding Cancer Vaccines


I know some of you are doing or are looking into Cancer Vaccines. This may help you.

Understanding Cancer Vaccines

A vaccine helps the body fight disease. Most people are familiar with vaccines for diseases like chicken pox or the flu. Vaccines (sometimes called vaccinations) help train the immune system to recognize and destroy harmful substances, such as bacteria or viruses, before they can cause disease.

There are two types of cancer vaccines: prevention vaccines and treatment vaccines. A prevention vaccine is given to a healthy person to prevent the development of a specific type of cancer. The U.S. Food and Drug Administration (FDA) has approved three vaccines for cancer prevention. Gardasil and Cervarix are two different vaccines that prevent infection with the human papillomavirus (HPV). A long-lasting infection with HPV can cause cervical cancer. (HPV is also thought to cause other types of cancer, but so far, the vaccine is only approved for cervical cancer.) The third approved vaccine prevents infection with the hepatitis B virus (HBV); long-term infection with HBV can lead to the development of liver cancer.

A cancer treatment vaccine is a type of immunotherapy. Immunotherapy, also called biologic therapy, helps the body’s immune system fight the cancer. A treatment vaccine may prevent cancer from coming back, destroy any remaining cancer cells after other types of treatment, or stop cancer cell growth. A cancer vaccine is designed to be specific, which means it is supposed to get rid of the cancerous cells and not the healthy cells. Most vaccines for cancer treatment are still in development and only available through a clinical trial (research study involving people). However, in 2010, the FDA approved sipuleucel-T (Provenge) for men with metastatic prostate cancer. Although it is often called a “vaccine,” it is not like getting a flu shot. Sipuleucel-T is an immunotherapy that is adapted for each individual patient. First, white blood cells are removed from the patient. They are then modified in a laboratory and infused back into the patient to allow the immune system to find and destroy prostate cancer cells. Researchers hope that having such therapy approved spurs the development and eventual approval of additional immunotherapies for cancer.

How a cancer vaccine works

The task of a person’s immune system is to tell the difference between something that is part of the body and a substance that is potentially harmful to the body, such as a virus. This identification is made through antigens, which are substances on the surface of cells that are not normally part of the body. The immune system recognizes the antigens and attacks them, typically eliminating them. Some immune system cells release specialized proteins called antibodies that help destroy the antigens. Other immune system cells may attack antigens directly, without the help of antibodies. The immune system is left with a “memory” that helps it respond to those antigens in the future.

A cancer vaccine takes advantage of the immune system’s response to antigens. Often, cancer cells have specific molecules or more numerous ones that are not present on healthy cells. When injected into a person, these specific molecules act as antigens, which stimulate the immune system to recognize and destroy cancer cells with these antigens. Most cancer vaccines also contain adjuvants, substances that may help improve the immune response.

There are two sources of antigens: those made from a patient’s cells and those from cells or proteins that are developed in a laboratory. A vaccine that is customized for each patient, such as sipuleucel-T, may be more effective because the antigens are specific to the patient’s tumor. However, they are also more expensive. A vaccine made in the laboratory may not be as specific for an individual patient, but are somewhat less expensive and may be easier to make.

Limitations of cancer vaccines

Developing successful cancer treatment vaccines is difficult. Some limitations of cancer vaccines are:

Cancer cells suppress the immune system—this is how the cancer is able to grow and develop in the first place. An adjuvant may help overcome this problem.

The immune system doesn’t always recognize that cancer cells are harmful. Because cancer cells develop from a person’s own healthy cells, they may not “look” harmful to the immune system. Instead of being eliminated, the cancer cells are ignored.

Larger or more advanced tumors are hard to destroy, especially with only a vaccine. This is a reason why cancer vaccines are given in addition to other treatments.

The immune systems of people who are sick may not be able to produce a good immune response. Also, a person’s immune system slows with age, limiting the effectiveness of the vaccine.
Because of these reasons, some researchers think that a cancer treatment vaccine may be more effective in patients with smaller tumors or early-stage cancers.

Vaccines and clinical trials

Several vaccines are being tested in clinical trials. According to the National Cancer Institute (NCI), vaccines for melanoma (both skin and ocular [eye]), leukemia, non-Hodgkin lymphoma, multiple myeloma, brain tumors, bladder cancer, kidney cancer, lung cancer, and pancreatic cancer are being evaluated in clinical trials. Usually, these vaccines are given in addition to other treatment, such as chemotherapy.

Clinical trials are important for learning more about cancer vaccines. Talk with your doctor about the possibility of a cancer vaccine clinical trial. Some questions to ask the doctor include:

What is the vaccine and how does it work?

How is this vaccine made?

How often is the vaccine given?

How long will I need the vaccine?

What are the possible side effects?

Is there another treatment option for this cancer?

Is there anything else I need to know?
More Information

ASCO Expert Corner: HPV Vaccination for Cervical Cancer

Understanding Immunotherapy

Additional Resources

National Cancer Institute: Treating and Preventing Cancer With Vaccines

National Cancer Institute: Cancer Vaccine Fact Sheet

"Knolwedge is power. The power to understand."

“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, August 16, 2010

Immune Cell Therapy –A Promising Approach For Treating Cancer

Immune Cell Therapy –A Promising Approach For Treating Cancer
August 15th, 2010

The new approach could dramatically improve the success rate of immune-cell therapies, which hold promise for treating many types of cancer, says Darrell Irvine, senior author of a paper describing the technique in the Aug. 15 issue of Nature Medicine.

“What we’re looking for is the extra nudge that could take immune-cell therapy from working in a subset of people to working in nearly all patients, and to take us closer to cures of disease rather than slowing progression,” says Irvine, associate professor of biological engineering and materials science and engineering and a member of MIT’s David H. Koch Institute for Integrative Cancer Research.

Details of the Study
To perform immune-cell therapy, doctors remove a type of immune cells called T cells from the patient, engineer them to target the tumor, and inject them back into the patient. Those T cells then hunt down and destroy tumor cells. Clinical trials are under way for ovarian and prostate cancers, as well as melanoma.

Although immune-cell therapy is a promising approach to treating cancer, success has been limited by difficulties in generating enough T cells that are specific to the cancer cells and getting those T cells to function properly in the patient.

To overcome those obstacles, researchers have tried injecting patients with adjuvant drugs that stimulate T-cell growth and proliferation. One class of drugs that has been tested in clinical trials is interleukins — naturally occurring chemicals that help promote T-cell growth but have severe side effects, including heart and lung failure, when given in large doses.

Irvine and his colleagues took a new approach: To avoid toxic side effects, they designed drug-carrying pouches made of fatty membranes that can be attached to sulfur-containing molecules normally found on the T-cell surface.

In the Nature Medicine study, the researchers injected T cells, each carrying about 100 pouches loaded with the interleukins IL-15 and IL-21, into mice with lung and bone marrow tumors. Once the cells reached the tumors, the pouches gradually degraded and released the drug over a weeklong period. The drug molecules attached themselves to receptors on the surface of the same cells that carried them, stimulating them to grow and divide.

Within 16 days, all of the tumors in the mice treated with T cells carrying the drugs disappeared. Those mice survived until the end of the 100-day experiment, while mice that received no treatment died within 25 days, and mice that received either T cells alone or T cells with injections of interleukins died within 75 days.

Irvine’s approach to delivering the adjuvant drugs is both simple and innovative, says Dranoff. “The idea of modifying T cells in the lab to make them work better is something many people are exploring through more complicated approaches such as gene modification,” he says. “But here, the possibility of just attaching a carefully engineered nanoparticle to the surface of cells could be a much simpler procedure.”

While he is now focusing on immune-cell therapy, Irvine believes his cell pouches could be useful for other applications, including targeted delivery of chemotherapy agents. “There are lots of people studying nanoparticles for drug delivery, especially in cancer therapy, but the vast majority of nanoparticles injected intravenously go into the liver or the spleen. Less than 5 percent reach the tumor,” says Irvine, who is also a Howard Hughes Medical Institute Investigator.

With a new way to carry drugs specifically to tumors, scientists may be able to resurrect promising drugs that failed in clinical trials because they were cleared from the bloodstream before they could reach their intended targets, or had to be given in doses so high they had toxic side effects.

Irvine and his colleagues also demonstrated that they could attach their pouches to the surface of immature blood cells found in the bone marrow, which are commonly used to treat leukemia. Patients who receive bone-marrow transplants must have their own bone marrow destroyed with radiation or chemotherapy before the transplant, which leaves them vulnerable to infection for about six months while the new bone marrow produces blood cells.

Irvine is now starting to work on making sure the manufacturing process will yield nanoparticles safe to test in humans. Once that is done, he hopes the particles could be used in clinical trials in cancer patients, possibly within the next two or three years.

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Massachusetts Institute of Technology. The original article was written by Anne Trafton, MIT News Office.

Journal Reference:

1. Matthias T Stephan, James J Moon, Soong Ho Um, Anna Bershteyn & Darrell J Irvine. Therapeutic cell engineering using surface-conjugated synthetic nanoparticles. Nature Medicine, 2010; DOI:10.1038/nm.2198


“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 BPhotobucket

The Perfect Storm..Therapeutic use of Anti-CTLA-4 Blockage and IL-2 to enhance T-cell responses in vivo

The Perfect Storm..Therapeutic use of Anti-CTLA-4 Blockage and IL-2 to enhance T-cell responses in vivo
Dr. Cassian Yee
Fred Hutchinson Cancer Research Center
Clinical Research
Program in Immunology
Member Appointed: 2009
University of Washington School of Medicine Medicine


Associate ProfessorAppointed: 2004
Fred Hutchinson Cancer Research Center
Immune Monitoring Laboratory
Director Appointed: 2003

In my studies, I contacted Dr. Cassian Yee about what I think would revolutionize Melanoma Treatment. Dr. Yee is noted for one of the first Scientists to harness the Immune system to fight Melanoma (2008).

"In what could be a breakthrough in cancer therapy, researchers report in The New England Journal of Medicine today that they succeeded in bolstering a patient's immune system enough to wipe out late-stage malignant tumors on its own. The scientists say the successful experiment could pave the way for new treatments of advanced cancer that spare patients the side effects of chemotherapy, which kills healthy as well as malignant cells."


Dear James,
i have not gone over in detail the information you sent, but i and think others will agree that anti-CTLA4 augments / lowers the threshold for a productive anti-tumor response once that is initiated in some form ('spark'). the role of aCTLA4 and Tregs is still not entirely worked out. I am glad that this has worked out well for you and with the emergence of immunotherapy in general as a treatment modality, with studies coming from Drs. Wolchok, Allison and others, we all hope that the
'Message keeps getting clearer'

Cassian Yee

As you can see by the reply, I think we are onto something big.

I don’t want to waste your time but I think this issue is of the utmost importance. Your Ipilimumab is the major factor in keeping the CD4+ T-cells activated, but it can’t do it alone.

"You need the tumor specific antigens, (The Keys), you need the (Spark Plug) Anti-CTLA-4 and you need the (Gas) IL-2. Without these three key components your car won’t run." ~jimmy B~

As a patient/survivor/researcher of stage IV Melanoma I have scientifically accounted for why my therapy has worked. Above are supporting documents and also a paper (draft) I have written that describes my treatment journey. Please, take time out of you busy schedule and take a look these documents. Bristol Meyer Squibb holds a very promising drug, and when administered in the correct timing and dose, can jumpstart the (Car) The Immune system.

I think they are making great strides in the fight against Melanoma

We need to put it into practice.

“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, August 2, 2010

This is what is keeping my Melanoma Lesion at bay ..Jim Breitfeller




Topical Imiquimod 2009


“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.