Poised for progress..Melanoma ..Jim Breitfeller

Poised for progress
By Bill Schaller

Dana-Farber Cancer Institute

Friday, September 17, 2010

A new focus on the immune system’s ability to both unleash and restrain its attack on disease has led scientists at Harvard-affiliated Dana-Farber Cancer Institute to identify cells in mice that prevent the immune system from attacking the animals’ own cells, protecting them from autoimmune diseases such as multiple sclerosis, Type 1 diabetes, and lupus.

The discovery, recently reported by the journal Nature, may give scientists an effective way of operating the immune system’s internal “control panel,” leading to improved therapies for a variety of diseases — from vaccines that prompt the immune system to stage a sustained assault on cancers, to treatments that derail the biological onslaught associated with autoimmune diseases. The fact that human immune system cells share key features with those in mice makes the prospect of such advances quite realistic, the study authors say.

“The traditional view of the immune system is of specialized groups of cells poised to attack foreign pathogens [disease-causing agents],” said senior author Harvey Cantor, the Baruj Benacerraf Professor of Pathology at Harvard Medical School and chair of the Department of Cancer Immunology and AIDS at Dana-Farber. “While that model is generally correct, we’ve come to appreciate that the immune system, like other complex biological information systems, includes a counterbalance mechanism — a set of cells programmed to suppress the immune response. Such cells are essential to preventing excessive reactions to pathogens and misguided attacks on the body’s own cells.”

The search for cells involved in quieting the immune response has previously focused on immune system cells known as CD4+ T cells, some of which have been shown to prevent abnormal inflammation in response to disease or infection. In the new study, lead author Hye-Jung Kim and her colleagues found that CD8+ T cells (known as killer T cells because of their ability to kill diseased cells) also include a subset that helps dampen the immune response. Instead of reducing inflammation like their CD4 cousins, the CD8+ T regulatory (CD8+Treg) cells ensure that the immune system doesn’t produce antibodies that attack normal cells.

The Dana-Farber team discovered how CD8+ Treg cells accomplish this feat. They mingle with cells known as follicular T-helper cells, which are intermediaries that prompt the immune system’s B cells to make disease-fighting antibodies. The meeting with CD8+ Treg cells essentially shuts off the follicular T-helper cells, preventing them from interacting with B cells. No interaction means no production of antibodies, which means no assault on an animal’s normal, healthy cells.

The critical point of contact between CD8+ Treg cells and follicular T-helper cells is a protein on the helper cells called Qa-1. When Kim and her colleagues bred a strain of mouse with abnormal Qa-1, the animals developed a form of lupus. The reason: the CD8+ Treg cells couldn’t latch onto the defective protein, leaving the follicular cells free to order the B cells to produce antibodies, some of which targeted the animals’ own tissue.

The significance of this work is that CD8+ Treg cells represent a new lever for raising or lowering the strength of the immune response. This class of cells, it turns out, depends for its survival on a cytokine (a regulatory compound) called interleukin 15. Increase the supply of CD8+ Treg cells and the immune response is suppressed — a potentially powerful way of dealing with autoimmune diseases. Decrease the amount of such cells and the immune response can be invigorated and extended — a useful complement to vaccines that unleash the immune system on cancer.

“Experience has shown that vaccines that simply activate or expand the number of T and B cells are not likely to result in a prolonged, robust anti-tumor response,” Cantor explains. “The balancing mechanism within the immune system means that when more disease-fighting cells are generated, there’s a countervailing increase in the number of immune-suppressing cells that are generated. The key is to break that loop. This work brings that goal closer.”

Source:http://news.harvard.edu/gazette/story/2010/09/poised-for-progress/

A Phase I Study of Intravenous Recombinant Human IL-15 in Adults With Refractory Metastatic Malignant Melanoma and Metastatic Renal Cell Cancer
It is recruiting.

A Phase I Study of Intravenous Recombinant Human IL-15 in Adults With Refractory Metastatic Malignant Melanoma and Metastatic Renal Cell Cancer

Maybe a combination of Anti-CTLA-4 blockage + IL-15 may be another protocol that will erradicate the Melanoma Tumor



“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

Using personalized vaccines, researchers enlist the immune system to oust tumors.Melanoma..Jim Breitfeller

Using personalized vaccines, researchers enlist the immune system to oust tumors.

Getting Personal
BY KATY HUMAN
In 2003, Stephen Creel, a manager at a software company in Austin, Texas, suddenly started passing blood in his urine. He had just celebrated his 40th birthday with friends and his wife, who was pregnant with their daughter, and he was as fit as he’d been in years.

The diagnosis of kidney cancer—renal cell carcinoma—was “shocking,” Creel says.

His father-in-law, a cancer researcher, directed Creel to M.D. Anderson Cancer Center in Houston, almost 170 miles away, where oncologists were testing an experimental vaccine to treat kidney cancer.

They surgically removed patients’ tumors, sent samples away for processing, and then re-injected cancer-specific proteins back into the patient. They were trying to activate the patients’ own immune system cells, train them to recognize cancer as an invader, and fight it off.


Using personalized vaccines, researchers enlist the immune system to oust tumors


What if you could get your body to immunize yourself against Melanoma?
You would just need your immune system to recognize the tumor antigen.
You need the tumor to shed the right antigenic protein

It can and has been done. I am one of those cases.
Take a look at my jounery in the papers below.

Melanoma and The Magic Bullet (Monoclonal Antibodies)


The Making of an Immune Response by Combinatorial Therapy Using Anti-CTLA-4 Blockade and Interleukin-2


Eureka!!!!!! A possible cure for Melanoma, the Deadly Skin Cancer




Take care

Jimmy B

Melanoma_Missionary


"Today might be the worst day of your life...but tomorrow could be the best. You just have to get there."
~Unknown~

Effective Immunotherapy for Patients with Metastatic Melanoma..Jim Breitfeller

Steven A. Rosenberg, MD, PhD
Chief of Surgery, National Cancer Institute
National Institutes of Health, Bethesda, MD

Immunotherapy has emerged as the most effective treatment for patients with metastatic melanoma. Much of the information concerning the immune response to melanoma has come from the study of tumor-infiltrating lymphocytes (TIL), immune cells that infiltrate into the stroma of the growing tumor and can be grown in vitro in the cytokine IL-2.1 TIL have been used to identify dozens of antigens that are presented on melanomas.2 Some antigens such as MART-1 and gp100 are shared by both melanomas and normal melanocytes, whereas others, such as NY-ESO-1, can be expressed on melanomas, but on no other adult tissue except the testes.

Most studies of immunotherapy for melanoma patients have been directed at those with metastatic disease. Although multiple trials of cancer vaccines have been performed in patients with resected lymph nodes at high risk of recurrence, none of these clinical trials have convincingly demonstrated prolonged survival.3 Some controversy exists surrounding the use of interferon alpha for the treatment of stage 3 melanoma; prolonged follow-up of patients in prospective randomized trials has yielded ambiguous results, and many oncologists are concluding that the toxicities of highdose interferon are not warranted given the lack of conclusive evidence of effectiveness in this setting.

Substantial progress has been made, however, in the treatment of patients with metastatic melanoma. It is now possible to cause complete regressions of widely metastatic melanoma at multiple sites in the body utilizing immunotherapy approaches. Immunotherapy Approaches To Metastatic Melanoma Approaches to the treatment of patients with metastatic melanoma fall into three major categories, which are summarized in Table 1 at Effective Immunotherapy for Patients with Metastatic Melanoma


Take care

Jimmy B


Melanoma_Missionary


"Today might be the worst day of your life...but tomorrow could be the best. You just have to get there."
~Unknown~

GM-CSF-based Second-generation Oncolytic Herpesvirus Vaccine Promising for Melanoma..Jim Breitfeller

GM-CSF-based Second-generation Oncolytic Herpesvirus Vaccine Promising for Melanoma

Researchers involved in an international multicenter clinical Phase II trial have reported a 26% response rate for patients with metastatic melanoma treated with a second-generation granulocyte-macrophage colony-stimulating factor (GM-CSF) oncolytic herpes simplex virus (HSV) vaccine. The details of this study were published in the December 1, 2009 issue of the Journal of Clinical Oncology.[1]

Melanoma is considered an immune responsive cancer. A small fraction of patients with metastatic disease respond to a variety of immune therapies including: Proleukin® (interleukin-2), lymphokine activated killer (LAK) cells, tumor infiltrating lymphocytes (TIL), and genetically manipulated T-cells. In addition, there have been many attempts to develop a successful vaccine.

A previous Phase I study of this second-generation oncolytic HSV expressing GM-CSF was carried out in patients with a variety of solid tumors. In this study the vaccine was called OncoVEX-GM-CSF and is made by BioVex.[2] This study established a safe dose, and responses were observed in patients with melanoma and other solid tumors.

The current study evaluated the same vaccine, which is called JS1/34.5/47-/GM-CSF, for the treatment of 50 patients with metastatic melanoma. Seventy-five percent of patients in this study had failed one or more systemic therapies. Vaccine was injected into tumor nodules every two weeks for up to 24 treatments, and some patients who responded or were stable were then treated on an extended protocol. These authors made the following observations:

The overall response rate was 26%.
Eight patients (16%) had a complete response.
Five patients (10%) had a partial response.
Responses occurred in injected and distant sites.
10 patients (20%) had stable disease for more than three months.
92% of responses were maintained for 7-31 months.
Two additional patients had a complete response after surgery.
Two additional patients with an initial partial response or stable disease achieved a complete response after 24 months of further vaccination.
Overall survival at one year was 58% and 52% at two years.
Comments: These are the best results achieved to date for any vaccine for melanoma. This study will by followed up by a Phase III study to confirm these results.

References:



--------------------------------------------------------------------------------

[1] Senzer JJ, Kaufman HL, Amatruda T, et al. Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. Journal of Clinical Oncology. 2009;27:5763-5771.

[2] Hu JC, Coffin RS, Davis CJ, et al: A phase I study of OncoVEXGM-CSF, a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor. Clin Cancer Res. 12:6737–6747, 2006.

Source:http://professional.cancerconsultants.com/oncology_main_news.aspx?id=44340



Take Care,

Jimmy B

The Top 5 Most Promising Upcoming Drugs for Melanoma..Jim Breitfeller

New Phase III Clinical Trials for the Treatment of Melanoma
From Timothy DiChiara, Ph.D., for About.com
Created: May 21, 2009

About.com Health's Disease and Condition content is reviewed by the Medical Review Board


Treatment of advanced (stage III and IV) melanoma is in desperate need of some good news. Although the incidence of melanoma is increasing by a whopping 3 to 5% per year in the United States, current therapies don't significantly increase survival in most patients and no new first-line medicines have been approved in over 10 years.
Clinical trials are the best hope for a long-lasting reduction or elimination of metastatic melanoma (called a "durable response" or "complete response" by doctors). The US National Institutes of Health lists 27 late-stage (phase III) clinical trials currently recruiting patients with melanoma. Many of the trials are testing new combinations of existing drugs, new ways to administer them, or new surgical procedures, but some are investigating brand new drugs. The most promising are the following:

Allovectin-7 - This novel gene therapy is injected directly into the tumors of patients with stage III or IV disease, which then alerts the body's own immune system to attack the tumor. Earlier trials of Allovectin alone showed that tumors in 4% to 9% of patients responded to the therapy. The new trial is comparing Allovectin-7 to the standard chemotherapy treatment, either dacarbazine or temzolomide. Made by Vical. Find out if you may qualify for the AIMM trial of Allovectin-7.

oblimersen (Genasense) - Genasense is a unique inhibitor of Bcl-2, a protein made by cancer cells that is thought to block chemotherapy-induced cell death (called "apoptosis"). So by reducing the amount of Bcl-2 in cancer cells, Genasense may enhance the effectiveness of current anticancer treatment. Previous studies demonstrated that Genasense combined with the chemotherapy drug dacarbazine tripled response rate and significantly increased overall survival compared to dacarbazine alone. Made by Genta. Find out more about the AGENDA trial of oblimersen.

MVax - MVax is a melanoma vaccine prepared from the patient's own cancer cells. Several studies have shown that MVax followed by interleukin-2 can lead to a complete response in up to 13% of patients, double that of interleukin-2 alone. MVax is also effective in patients with stage III melanoma when given post-surgery: it doubled the 5-year survival rate compared to surgery alone. Made by AVAX Technologies. Find out more about the MVALDI trial for MVax.

ipilimumab (MDX-010, MDX-101, or BMS-734016) - Ipilimumab is an antibody that activates the body's immune system to fight melanoma by inhibiting the CTLA-4 molecule. Three previous phase II clinical trials have shown that treatment with ipilimumab results in a one-year survival rate of 47% to 51% for people with stage III or IV melanoma, which is almost double the average. The current trial is comparing ipilimumab to a dummy treatment (placebo) in patients with stage III melanoma who have already undergone surgery. Made by Medarex and Bristol-Myers Squibb. Find out more about the EORTC 18071 trial for ipilimumab.

OncoVEXGM-CSF - OncoVEXGM-CSF is a vaccine that works by spreading within tumors and causing the death of cancer cells while stimulating the immune system to destroy metastatic tumors. Previous results from 50 patients with inoperable stage IIIc/IV melanoma demonstrated that 28% of patients responded, including 12% with a complete response. The new trial is enrolling patients with previously treated but inoperable stage IIIb, IIIc or IV melanoma and is designed to compare OncoVEXGM-CSF to a naturally-occurring substance in the body called a "granulocyte monocyte colony stimulating factor" (GM-CSF), which increases white blood cells. Made by BioVex. Find out more about the trial for OncoVEXGM-CSF.

Why Participate in Clinical Trials

Those who take part in clinical trials get access to the latest treatments that are often not available anywhere else. These treatments may be better than the standard of care and may offer the only hope for those with advanced disease. Simply put, participation in clinical trials by patients like you is the only way research will advance toward an eventual cure for melanoma.

Talk about the possibilities with your doctor!

Source:

ClinicalTrials.gov. US National Institutes of Health. 10 February 2009.

Take Care,

Jimmy B

World first: Vaccine helps prevent HIV infection..Melanoma..Jim Breitfeller

World first: Vaccine helps prevent HIV infection

Two vaccines that did not work as a single agent, but combine them and they have 30% efficacy.

Read more: http://www.sfgate.com/cgi-bin/article.cgi?f=/n/a/2009/09/23/international/i224743D59.DTL&tsp=1#ixzz0S3Jo5WE0


What does HIV have to do with Melanoma?

HIV is an Immune System problem. It has to deal with your CD4+ T cells.

ARE YOU SEEING MY CORRELATION YET? We as Melanoma Patients need to activate our CD4+ T cells.

Interluekin-2 and Anti-CTLA-4 both have a low efficacy. But if you combine the two, with the right timing and dose, you will see synergistic results. The Final step is to get the right tumor specific antigen so the Cytotxic T- Cell can hone in on the tumors.

Here is an Email I just recieved:

"I asked my doc yesterday his opinion of your theory - IL2 + ipi = NED. He is in total agreement, and has seen it firsthand as well. He says he is actively pushing, but that he doesn't see it becoming available until next fall. AUGHHH!!!! So frustrating."

There is HOPE!!!!!!!




Take Care,

Jimmy B

The Word is Finally Out on How to Use IL-2 Effectively..Melanoma ..Jim Breitfeller

Vaccine cocktail might be more effective against certain cancers
Researchers are giving vaccines in combination with other drugs either to help boost the immune response or to attack the cancer on multiple fronts.

By Jill U. Adams

July 6, 2009 Even if a vaccine produces an appropriate cancer-attacking immune response, it still may not be enough to achieve clinical benefit, especially in patients with very advanced disease.

This could be because the ability of large tumors to suppress the patient's immune system is stronger than the vaccine's effect.


Or it could be because very sick patients may not have healthy enough immune systems to respond to the vaccine.

Now researchers are giving vaccines in combination with other drugs -- either to help boost the immune response or to help attack the cancer on multiple fronts. And they are more careful in selecting patients who might benefit from vaccine therapy.

For example, the new melanoma vaccine (which uses a fragment of a protein called gp100) is given in combination with the immune stimulant interleukin-2, which serves as a growth factor for immune cells, says Dr. Douglas Schwartzentruber, medical director at the Goshen Center for Cancer Care in Goshen, Ind., who presented the clinical trial results at last month's conference.


"It causes the lymphocytes to multiply in large numbers," Schwartzentruber says. "So you can specifically train this lymphocyte to recognize this cancer, and then you can multiply it with the interleukin-2."

Interleukin-2 also happens to be an FDA-approved treatment for melanoma. With that drug alone, up to 15% of patients will see their tumors shrink. "That's as good as anything out there, frankly, for metastatic melanoma," Schwartzentruber says. Of the 185 patients in his clinical trial, 10% saw their tumors shrink with interleukin-2 alone and 22% saw the same with the combination of interleukin-2 plus vaccine.

With the new lymphoma vaccine, which also uses an immune stimulant to boost the response of immune cells, the results were more robust. In the latest trial, 117 patients who had received chemotherapy were followed for five years, on average. Those who received the vaccine -- made using a marker from patients' own cancer cells -- were cancer-free for 44 months, on average. Those who didn't get the vaccine were cancer free for 31 months.

The Provenge trial included 512 men who had advanced prostate cancer that was not responsive to hormone therapy, a standard treatment for prostate cancer. The vaccine differs from the others in that a patient's own immune cells are removed, fitted with a marker for prostate cancer (called prostatic acid phosphatase or PAP), and injected back into the patient. Three-year survival rates were 31% for vaccinated subjects and 23% for control subjects.

Provenge is considered the vaccine closest to the finish line, but FDA approval is by no means a sure thing. Any number of concerns might arise with close scrutiny of the data, says Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society in Atlanta. The FDA could find problems in the control group that muddy interpretation of the outcome or it might argue that effects on disease progression are as important as survival rates. Provenge has not been reported to slow progression of disease.

Source:http://www.latimes.com/features/health/la-he-vaccineside6-2009jul06,0,3888682.story

If you have read my Paper "Melanoma and the Magic Bullet (Monoclonal antibodies)", You would see how to use HD IL-2 effectively in Melanoma therapy. I Have been preaching it; is all in the timing and dose.

Take Care,

Jimmy B

Experimental Vaccine Improves Melanoma Outcomes..Melanoma ..Jim Breitfeller

Experimental Vaccine Improves Melanoma Outcomes

By CancerConsultants.com

Patients with advanced melanoma experienced higher response rates and longer survival without cancer progression when treated with an experimental anticancer vaccine in addition to standard therapy. These were the preliminary findings from a Phase III clinical trial presented at the 2009 annual meeting of the American Society of Clinical Oncology (ASCO).

Patients with metastatic melanoma are usually treated with a combination of chemotherapy and immunotherapy. Chemotherapeutic agents with activity include dacarbazine, temozolomide, cisplatin, vinblastine, thalidomide, and docetaxel. Immunotherapy agents include interferon-alfa (INF-alfa) and Proleukin® (interleukin-2,IL-2). However, because most therapy is palliative, tolerability of treatment is a significant factor. Recently, researchers have emphasized the development of tolerable regimens.

Proleukin in high doses is an FDA-approved drug for the treatment of metastatic melanoma. However, Proleukin produces responses in only a minority of patients and at high doses is associated with significant toxicities. There have been innumerable studies performed over the past two decades to improve the response rate and decrease the toxicities of Proleukin-based regimens for the treatment of melanoma. Despite all of these efforts, biologic therapy or combined biologic and chemotherapy still benefit only a minority of patients with melanoma. Various vaccines have been tested in patients with melanoma, but none have been approved for this use by the U.S. Food and Drug Administration.

In the current study, researchers evaluated an experimental anticancer vaccine known as gp100:209-217(210M) peptide. The vaccine acts by stimulating T cells to attack melanoma cells. This study enrolled 185 patients with Stage IV or locally advanced Stage III melanoma. Study participants were assigned to receive treatment with Proleukin alone or with Proleukin plus the vaccine.

Follow-up is not yet complete, but the following results were presented at ASCO:

•The overall response rate was 22% for patients treated with Proleukin plus the vaccine compared with 9.7% for patients treated with Proleukin.

•Progression-free survival was 2.9 months among patients treated with IL-2 plus the vaccine compared with 1.6 months among patients treated with Proleukin alone.

•Overall survival was 17.6 months among patients treated with Proleukin plus the vaccine compared with 12.8 months among patients treated with Proleukin alone. The difference between groups in overall survival did not meet the criteria for statistical significance.

•The vaccine was well tolerated. Side effects were swelling and redness at the injection site.


Comments: This study is one of the first to show promising results for vaccine in metastatic melanoma. Researchers will continue to follow the patients enrolled in the study to assess longer-term results.





Reference: Schwartzentruber DJ, Lawson D, Richards J et al. A phase III multi-institutional randomized study of immunization with the gp100:209-217(210M) peptide followed by high-dose IL-2 compared with high-dose IL-2 alone in patients with metastatic melanoma. Journal of Clinical Oncology. 2009;27:15s, abstract CRA9011.




Study Type: Interventional

Study Design: Treatment, Randomized, Active Control

Official Title: A Phase III Multi-Institutional Randomized Study of Immunization With the GP100: 209-217 (210M) Peptide Followed by High Dose IL-2 vs. High Dose IL-2 Alone in Patients With Metastatic Melanoma

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
•Whether the addition of peptide vaccine to high-dose aldesleukin is superior to alaldesleukin alone by response rates after each course of treatment [ Designated as safety issue: No ]


Secondary Outcome Measures:
•Toxicity of treatment by NCI Common Toxicity Criteria after each course of treatment [ Designated as safety issue: Yes ]

•Disease-free and progression-free survival comparison by disease evaluation every 3 months after treatment [ Designated as safety issue: No ]

•Immunologic response to treatment by various laboratory studies before and after each course of treatment [ Designated as safety issue: No ]

•Quality of life by Functional Assessment of Chronic Illness Therapy Fatigue Subscale RSF-36 SDS before and after the first course of treatment [ Designated as safety issue: No ]



Do you reconize the graph, you should . Now Look closely at the timing of the addition of IL-2. Do you see a major problem?????

It (IL-2) is being added before and close to the maximum propgation of the CD4+ T cells. This means they are growing the Tregs cells which we want to deplete or surpress.

VERY INTERESTING to say the Least...

Take care

Jimmy B


Melanoma_Missionary


Take Care,

Jimmy B

Experts Optimistic About Melanoma vaccine.. Melanoma..Jim Breitfeller

tPhase 3 study reports improved survival for those with advanced disease,,

SATURDAY, May 30 (HealthDay News) --A vaccine for advanced melanoma has shown promise in a new study.

Melanoma is the most serious type of skin cancer. The five year-survival rates for local and metastatic melanoma are 65 percent and 16 percent, respectively. In 2009, an estimated 69,000 people in the United States will be diagnosed with melanoma and about 8,600 will die of the disease, according to the American Cancer Society.

The study, a phase 3 clinical trial involving 185 people, found that using the peptide vaccine in combination with the immunotherapy drug Interleukin-2 improved response rates and progression-free survival, according to University of Texas M.D. Anderson Cancer Center researchers, who said it was the first phase 3 trial to show a clinical benefit in a vaccine for melanoma.

Response rate and progression-free survival were 22.1 percent and 2.9 months, respectively, in people given the vaccine, compared with 9.7 percent and 1.6 months for those who were not vaccinated. Median overall survival was 17.6 months for the vaccine group and 12.8 months for the others.

The study, which was to be presented Saturday at the annual meeting of the American Society of Clinical Oncology in Orlando, Fla., was funded in part by Novartis, which makes Interleukin-2.

"Obviously this is a disease, in its advanced setting, in need of better therapies for our patients," study co-author Dr. Patrick Hwu, a professor and chairman of M.D. Anderson's Department of Melanoma Medical Oncology, said in a news release from the center.

"While more follow-up is needed, this study serves as a proof-of-principle for vaccines' role in melanoma and in cancer therapy overall," Hwu said. "If we can use the body's own defense system to attack tumor cells, we provide a mechanism for ridding the body of cancer without destroying healthy tissue."

The vaccine, called gp100:209-217 (200M), works by stimulating T-cells, which control immune response.

"This vaccine activates the body's cytotoxic T-cells to recognize antigens on the surface of the tumor," Hwu said. "The T-cells then secrete enzymes that poke holes in the tumor cell's membrane, causing it to disintegrate."

Source:http://www.bio-medicine.org/medicine-news-1/Experts-Optimistic-About-Melanoma-Vaccine--47378-1/

Cutting Edge Technology “Infection-mimicking materials to program dendritic cells in situ”Melanoma .. Jim Breitfeller

Cutting Edge Technology “Infection-mimicking materials to program dendritic cells in situ”

Thanks to Donald Bohlken for bring this to my attention.

“I thought you might be interested in that attached article from the January 25, 2009 issue of the journal "Nature Materials" concerning a Harvard study of a new vaccine methodology which resulted in a 90% survival of mice infected with a melanoma strain which would normally kill them in 25 days. The article speaks of this result as a "cure".

The article synopsis notes: "Cancer vaccines typically depend on cumbersome and expensive manipulation of cells in the laboratory, and subsequent cell transplantation leads to poor lymph-node homing and limited efficacy. We propose that materials mimicking key aspects of bacterial infection may instead be used to directly control immune-cell trafficking and activation in the body. It is demonstrated that polymers can be designed to first release a cytokine to recruit and house host dendritic cells, and subsequently present cancer antigens and danger signals to activate the resident dendritic cells and markedly enhance their homing to lymph nodes. Specific and protective anti-tumour immunity was generated with these materials, as 90% survival was achieved in animals that otherwise die from cancer within 25 days. These materials show promise as cancer vaccines, and more broadly suggest that polymers may be designed to program and control the trafficking of a variety of cell types in the body."
This is Nano and Transdermal Technology at its best.

Implants Mimic Infection To Rally Immune System Against TumorsMain Category:

Melanoma / Skin CancerAlso Included In: Immune System / Vaccines; Medical Devices / Diagnostics; Biology / Biochemistry

Article Date: 25 Jan 2009 - 0:00 PST

“Bioengineers at Harvard University have shown that small plastic disks impregnated with tumor-specific antigens and implanted under the skin can reprogram the mammalian immune system to attack tumors.

The research -- which ridded 90 percent of mice of an aggressive form of melanoma that would usually kill the rodents within 25 days -- represents the most effective demonstration to date of a cancer vaccine.

Harvard's David J. Mooney and colleagues describe the research in the current issue of the journal Nature Materials.

"Our immune systems work by recognizing and attacking foreign invaders, allowing most cancer cells -- which originate inside the body -- to escape detection," says Mooney, Gordon McKay Professor of Bioengineering in Harvard's School of Engineering and Applied Sciences. "This technique, which redirects the immune system from inside the body, appears to be easier and more effective than other approaches to cancer vaccination."

Most previous work on cancer vaccines has focused on removing immune cells from the body and reprogramming them to attack malignant tissues. The altered cells are then reinjected back into the body. While Mooney says ample theoretical work suggests this approach should work, in experiments more than 90 percent of the reinjected cells have died before having any effect.
The implants developed by Mooney and colleagues are slender disks measuring 8.5 millimeters across. Made of an FDA-approved biodegradable polymer, they can be inserted subcutaneously, much like the implantable contraceptives that can be placed in a woman's arm.
The disks are 90 percent air, making them highly permeable to immune cells. They release cytokines, powerful attractants of immune-system messengers called dendritic cells.
These cells enter an implant's pores, where they are exposed to antigens specific to the type of tumor being targeted. The dendritic cells then report to nearby lymph nodes, where they activate the immune system's T cells to hunt down and kill tumor cells throughout the body.”

Source: Http://www.medicalnewstoday.com/articles/136473.php

Implants Mimic Infection To Rally Immune System Against Tumors



Donald Bohlken actually contacted one of the collaborators, Dr. Glenn Dranoff of the Dana Farber Cancer Institute and Harvard Medical School. He indicated: "We are initiating efforts to bring this to clinical testing, but it will take some time to adapt the procedures to patients. A one year time frame is a reasonable guess."

If this crosses over from the mouse model to the human model, we may have a winner on our hands. A 90 % response and if they are complete responses, this technology would surpass any therapy out there to date. The main take away is that they are prompting our immune system to recognize the tumors by activation of the T-cell. Rosenberg and Hwu and other colleagues are doing just that with (ACT) Adoptive Cell Transfer. Kirkwood, Camacho, Webber, Hodi, Maker, O’Day and Wolchok did that with anti-CTLA-4 blockage.

I can see the Light at the end of the tunnel!!!!!!!!!!!!!!!!!!!!!!!!!!!

Thank you Don for advocating for us and your Brother Ron who is a fighting Warrior of Melanoma.

I will post the research paper on Melanoma Missionary for everybody.

Jimmy B

Jay Tenenbaum Urges Collaboration To Treat the Long Tail of Disease Melanoma..Jim Breitfeller

By Kevin Davies

February 26, 2009 SAN FRANCISCO—In the powerful opening keynote at CHI’s Molecular Medicine Tri-Conference on Wednesday, Jay “Marty” Tenenbaum, founder and chairman of CollabRx, urged members of the life sciences community to share their resources to empower personalized research and help satisfy the unmet medical needs of the “long tail” of disease. “As a patient… I want to tap all of the world’s knowledge and all of the world’s resources into curing my disease,” Tenenbaum said.

Tenenbaum, a highly successful Internet entrepreneur in the 1990s, is a cancer survivor. Ten years ago, suffering from metastatic melanoma, he was given 12 months to live. He researched various experimental drug treatments, and credits a failed cancer vaccine, among other drugs, for saving his life. Through the company he founded, CollabRx, Tenenbaum aims to leverage the extraordinary untapped expertise and resources across the industry to empower individual patient healthcare through personalized research.

This sounds Familiar!!!!!!!!!


Source:http://www.bio-itworld.com/2009/02/26/tenenbaum-mmtc-keynote.html

Jay Tenenbaum Urges Collaboration To Treat the Long Tail of Disease


http://podcast.mktw.net/wsj/audio/20080728/pod-wsjmarcus/pod-wsjmarcus.mp3
Jay Tenenbaum Urges Collaboration Podcast


Take care

Jimmy B