New drug can increase life for Melanoma patients
Source: Dr. Jay Adlersberg
NEW YORK (WABC) -- A new treatment can extend the life of patients with melanoma skin cancer, which has spread to other parts of the body.
The breakthrough treatment came from a lab. Bruce Shewmaker, who is 64 years old, and his family put their fate in the lab's hands. In 2000, Shewmaker found a malignant melanoma.
"It started with just a blemish on my foot that had been there for 10 years and & one day it changed," Shewmaker said.
The cancer was removed surgically and he had 6 good years. However, by 2006, the cancer returned and was found in his lungs. Chemotherapy and other treatments failed. Each failure was a blow to Shewmaker.
"It's hard to maintain your hope that you're going to get through this," he said.
Getting through late stage cancer was also the hope of Dr. Jim Allison of Memorial Sloan Kettering Center. He did experiments in mice with late stage melanoma, using a new untested drug. After some disappointments, one day he was startled.
"In one group of mice the tumors quit growing and it was a eureka moment for sure, it was very exciting," he said.
Dr. Allison's experiments led to a drug for humans called Ipilimumab, IPI for short.
“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
This is Jim Breitfeller's journey into the Maze of Melanoma. Jim Breitfeller has gathered medical information for the patient and the caregiver. As Lance Armstrong would say "Lets stand Up to Cancer" Jim's Battle with the Beast July 2005 to present.
Friday, June 25, 2010
Wednesday, June 16, 2010
Grapgic Update.. New Pieces to the Melanoma Puzzle ..Jim Breitfeller
Take a look at this updated graphic. Notice that the upregulation of the CTLA-4 receptor is at it's max about 3 days after T-cell activation. These receptors must be blocked to surpress the Treg function.
“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
Saturday, June 12, 2010
CTLA-4 Ligation Blocks CD28-dependent T Cell Activation..Melanoma.Jim Breitfeller
CTLA-4 Ligation Blocks CD28-dependent T Cell Activation
Summary:
CTLA-4 is a CD28 homologue beheved to be a negative regulator of T cell function. However, the mechanism of this downregulatory activity is not well understood. The present study was designed to examine the effect of CTLA-4 ligation on cytokine production, cell survival, and cell cycle progression. The results demonstrate that the primary effect of CTLA-4 ligation is not the induction ofapoptosis. Instead, CTLA-4 signaling blocks IL-2 production, IL-2 receptor expression, and cell cycle progression of activated T cells. Moreover, the effect of CTLA-4 signaling was manifested after initial T cell activation. Inhibition oflL-2 receptor expression and cell cycle progression was more pronounced at late (72 h) time points after initial activation. The effects of anti-CTLA-4 mAbs were most apparent in the presence of optimal CD28-mediated costimulation consistent with the finding that CTLA-4 upregulation was CD28-dependent. Finally, the addition of exogenous IL-2 to the cultures restored IL-2 receptor expression and T cell prohferation. These results suggest that CTLA-4 signaling does not regulate cell survival or responsiveness to IL-2, but does inhibit CD28-dependent IL-2 production.
CTLA-4 Ligation Blocks CD28-dependent T Cell Activation
“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
Summary:
CTLA-4 is a CD28 homologue beheved to be a negative regulator of T cell function. However, the mechanism of this downregulatory activity is not well understood. The present study was designed to examine the effect of CTLA-4 ligation on cytokine production, cell survival, and cell cycle progression. The results demonstrate that the primary effect of CTLA-4 ligation is not the induction ofapoptosis. Instead, CTLA-4 signaling blocks IL-2 production, IL-2 receptor expression, and cell cycle progression of activated T cells. Moreover, the effect of CTLA-4 signaling was manifested after initial T cell activation. Inhibition oflL-2 receptor expression and cell cycle progression was more pronounced at late (72 h) time points after initial activation. The effects of anti-CTLA-4 mAbs were most apparent in the presence of optimal CD28-mediated costimulation consistent with the finding that CTLA-4 upregulation was CD28-dependent. Finally, the addition of exogenous IL-2 to the cultures restored IL-2 receptor expression and T cell prohferation. These results suggest that CTLA-4 signaling does not regulate cell survival or responsiveness to IL-2, but does inhibit CD28-dependent IL-2 production.
CTLA-4 Ligation Blocks CD28-dependent T Cell Activation
“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
Labels:
anti-CTLA-4 blockade,
IL-2,
interlukin-2,
T-cell activators
Master Combination..Melanoma.. Jim Breitfeller
Melanoma Therapy is like a combination Lock. You need three drugs, they must be in the right sequence to open the door to your immune system
1). Chemo/Radiation to shed dead tumor cells to be taken up by Dentritic Cells (DCs) as
antigen presenting Cells (APCs)
2).Anti-CTLA-4/AntiPD-1 Blockade to keep the activation on and suppress the Tregs
cells function.
3). Interluekin-2 for the activation, maintain their cytotoxic function, and their survival
The end result, the unleashing of the host’s Immune system on the cancer at large
“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, June 11, 2010
Pittsburgh Trip (06/28/06) in detail:How my Melanoma Journey Began..Jim Breitfeller
Pittsburgh Trip (06/28/06) in detail:
We left Rochester 4:00 am and arrived in Pittsburgh about 9:00 am. It’s a 5 hour trip if there are no detours along the way and you have a lead foot. I was very anxious to find out what my four options were so we had a cup of coffee and a croissant at their café and then proceeded to the doctor’s office. It was now about 9:30 am and my appointment was for 10:00 am. You know me, I like to be early. My wife says I am always too early. We proceeded to check in, and they gave me the normal treatment. They took my height, weight and vital signs. But this time they make a big deal about my weight. I had loss 4 lbs. So she calls over another nurse to retake my weight again (SOP) standard operating procedure. It was still short 4 lbs. I am thinking great, I am finally getting my weight under control. So, I turned to the nurses and said, “If you gave out cookies, you would not have these problems.” From their point of view, if you lose weight the cancer is active. Meanwhile, I’m thinking to myself, “Of course I lost weight. I’ve been so nervous. . . And, I just drove 291 miles without my breakfast. And we did make a couple of stops along the way.
Anyway, within 15 minutes we were called into the exam room. I am thinking this is great. The temperature in the room must have been 55 degrees. I was told to strip down to my underwear and put on one of those gowns with the slit up the back. I’m thinking, if this is anything like the last visit, I will freeze to death before anyone sees me. So, I told my wife, “If within 30 minutes, no one shows up, I’m going to put my clothes back on.” She said to me, that she was so cold that she had to go to the bathroom. So here we are, I’m shivering and my wife is crossing her legs to hold it in. So we are sitting and waiting, sitting and freezing for about 20 minutes. I did put my shoes back on to keep my feet warm.
Finally, the physician assistant steps into the room and greets us with a big “Hello!!!! ” She proceeds to tell us a little bit about the options, but then stops abruptly. She said: “the doctor should fill you in with all the details.” She then takes a look at my back, and with her hand, finds the lumps and starts counting them. She said “Good they are all there.” I am thinking, where the hell would they go, maybe on vacation? Nahhhhhhhhhhhh!
Anyway, no new lumps to report. She leaves the room to get the doctor and my wife follows her to find the bathroom. Dee returns relieved, just in time here hear a knock at the door.
In walks Dr. Kirkwood who greets us with a big smile and a hand shake. He asks us if Melissa, the physician assistant, has filled us in with the option details and could we go over the details with him to make sure we understood them. My wife and I turned to each other and our faces must have looked white to him. We tried to regurgitate what little information she had shared, although, it was VERY brief and we had not taken any notes. Melissa had told us that the doctor was going to go over the details. Well, my quick thinking wife said that Melissa gave us a very, very brief overview and that at our last meeting with him, we got all of 5 minutes of his time. I guess Dr. Kirkwood did not realize that the last time he had talked to us was before he had the PET/CT scans results and the options were different.
Anyway, he began to draw us a flowchart of the options on the exam table paper. He was really getting into it.
He started with the options at the top, and continued with the first line, second line and third line of defense therapy. It looked like an ISO document. I could draw it for you, but you’d probably fall asleep reading it. The worse part is, you have to have the therapies done in a certain sequence or you can not move to the next line of defense. Another problem, you can not mix and or match. To make things even worse, one of the better lines of defense had to be removed because I have the wrong blood type for the vaccine therapies. I was hoping to use this as my third line of defense.
My wife and I just sat there staring at the flowchart for what seemed like hours. We both started to run different scenarios in our head. We came up with the same conclusion. We needed a therapy that would allow us to “work outside the box” and not “cuff my hands”. We wanted to have the Ticilimumab/ Tremelimumab (from Pfizer …anti-CTLA-4 therapy as my second line of defense. CTLA-4 seems to slow down the immune response, so blocking it with an anti-CTLA-4 antibody may make the immune response more active.
Soooooooooooo! I signed my life away for the phase I study of Patrin in combination with dacarbazine under our protocol 03-091, which is currently not a nationally available trial.
I also signed up to allow Tumor Biopsies. Hey why not. It is FREEEEEEEE!!!! And I get two tumors removed for the price of one. And they say nothing is free in the world anymore. They will remove one and study it before treatment, and then take another one out and see what effect the chemo had on it during the first cycle of therapy. You know me I am always looking for a bargain--and, I am always doing some sort of research.
That is it from my end to yours. That sounds gross. Anyway take care, and keep those messages coming.
If you want to follow my journey you can read it here or at Carepages.com with comments.
http://www.carepages.com/carepages/jimmyBreitfeller
We needed a therapy that would allow us to “work outside the box” and not “cuff my hands”. We wanted to have the Ticilimumab/Tremelimumab (from Pfizer …anti-CTLA-4 therapy) as my second line of defense. CTLA-4 seems to slow down the immune response, so blocking it with an anti-CTLA-4 antibody may make the immune response more active.
That was then, This is Now, NED!!!
"Think Outside the Box"
“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
We left Rochester 4:00 am and arrived in Pittsburgh about 9:00 am. It’s a 5 hour trip if there are no detours along the way and you have a lead foot. I was very anxious to find out what my four options were so we had a cup of coffee and a croissant at their café and then proceeded to the doctor’s office. It was now about 9:30 am and my appointment was for 10:00 am. You know me, I like to be early. My wife says I am always too early. We proceeded to check in, and they gave me the normal treatment. They took my height, weight and vital signs. But this time they make a big deal about my weight. I had loss 4 lbs. So she calls over another nurse to retake my weight again (SOP) standard operating procedure. It was still short 4 lbs. I am thinking great, I am finally getting my weight under control. So, I turned to the nurses and said, “If you gave out cookies, you would not have these problems.” From their point of view, if you lose weight the cancer is active. Meanwhile, I’m thinking to myself, “Of course I lost weight. I’ve been so nervous. . . And, I just drove 291 miles without my breakfast. And we did make a couple of stops along the way.
Anyway, within 15 minutes we were called into the exam room. I am thinking this is great. The temperature in the room must have been 55 degrees. I was told to strip down to my underwear and put on one of those gowns with the slit up the back. I’m thinking, if this is anything like the last visit, I will freeze to death before anyone sees me. So, I told my wife, “If within 30 minutes, no one shows up, I’m going to put my clothes back on.” She said to me, that she was so cold that she had to go to the bathroom. So here we are, I’m shivering and my wife is crossing her legs to hold it in. So we are sitting and waiting, sitting and freezing for about 20 minutes. I did put my shoes back on to keep my feet warm.
Finally, the physician assistant steps into the room and greets us with a big “Hello!!!! ” She proceeds to tell us a little bit about the options, but then stops abruptly. She said: “the doctor should fill you in with all the details.” She then takes a look at my back, and with her hand, finds the lumps and starts counting them. She said “Good they are all there.” I am thinking, where the hell would they go, maybe on vacation? Nahhhhhhhhhhhh!
Anyway, no new lumps to report. She leaves the room to get the doctor and my wife follows her to find the bathroom. Dee returns relieved, just in time here hear a knock at the door.
In walks Dr. Kirkwood who greets us with a big smile and a hand shake. He asks us if Melissa, the physician assistant, has filled us in with the option details and could we go over the details with him to make sure we understood them. My wife and I turned to each other and our faces must have looked white to him. We tried to regurgitate what little information she had shared, although, it was VERY brief and we had not taken any notes. Melissa had told us that the doctor was going to go over the details. Well, my quick thinking wife said that Melissa gave us a very, very brief overview and that at our last meeting with him, we got all of 5 minutes of his time. I guess Dr. Kirkwood did not realize that the last time he had talked to us was before he had the PET/CT scans results and the options were different.
Anyway, he began to draw us a flowchart of the options on the exam table paper. He was really getting into it.
He started with the options at the top, and continued with the first line, second line and third line of defense therapy. It looked like an ISO document. I could draw it for you, but you’d probably fall asleep reading it. The worse part is, you have to have the therapies done in a certain sequence or you can not move to the next line of defense. Another problem, you can not mix and or match. To make things even worse, one of the better lines of defense had to be removed because I have the wrong blood type for the vaccine therapies. I was hoping to use this as my third line of defense.
My wife and I just sat there staring at the flowchart for what seemed like hours. We both started to run different scenarios in our head. We came up with the same conclusion. We needed a therapy that would allow us to “work outside the box” and not “cuff my hands”. We wanted to have the Ticilimumab/ Tremelimumab (from Pfizer …anti-CTLA-4 therapy as my second line of defense. CTLA-4 seems to slow down the immune response, so blocking it with an anti-CTLA-4 antibody may make the immune response more active.
Soooooooooooo! I signed my life away for the phase I study of Patrin in combination with dacarbazine under our protocol 03-091, which is currently not a nationally available trial.
I also signed up to allow Tumor Biopsies. Hey why not. It is FREEEEEEEE!!!! And I get two tumors removed for the price of one. And they say nothing is free in the world anymore. They will remove one and study it before treatment, and then take another one out and see what effect the chemo had on it during the first cycle of therapy. You know me I am always looking for a bargain--and, I am always doing some sort of research.
That is it from my end to yours. That sounds gross. Anyway take care, and keep those messages coming.
If you want to follow my journey you can read it here or at Carepages.com with comments.
http://www.carepages.com/carepages/jimmyBreitfeller
We needed a therapy that would allow us to “work outside the box” and not “cuff my hands”. We wanted to have the Ticilimumab/Tremelimumab (from Pfizer …anti-CTLA-4 therapy) as my second line of defense. CTLA-4 seems to slow down the immune response, so blocking it with an anti-CTLA-4 antibody may make the immune response more active.
That was then, This is Now, NED!!!
"Think Outside the Box"
“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
Labels:
dr. kirkwood,
DTIC,
ipilimumab,
patrin,
Tremelimumab
Thursday, June 10, 2010
Schuchter: Drug Rivals Work Together to Battle Melanoma - CNBC..Jim Breitfeller
Schuchter: Drug Rivals Work Together to Battle Melanoma - CNBC
“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
Labels:
cnbc,
Dr. Hodi,
Dr. Jedd D. Wolchok,
Dr. O'Day,
Dr. Schuchter,
ipilimumab
Dr. Keith T. Flaherty,reviews a landmark phase III study investigating ipilimumab..Melanoma..Jim Breitfeller
Dr. Keith T. Flaherty,reviews a landmark phase III study investigating ipilimumab in patients with previously treated, unresectable stage III or IV melanoma.
Keith T. Flaherty, MD, reviews a landmark phase III study investigating ipilimumab in patients with previously treated, unresectable stage III or IV melanoma.
Source:http://www.clinicaloptions.com/Oncology
“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
Labels:
BMS,
BMY,
Bristol-Meyer Squibb,
Clinical Care Options,
Dr. Flaherty,
ipilimumab
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma..Jim Breitfeller
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Published at www.nejm.org June 5, 2010 (10.1056/NEJMoa1003466)
The New England Journal of Medicine
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
“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
Published at www.nejm.org June 5, 2010 (10.1056/NEJMoa1003466)
The New England Journal of Medicine
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
“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, June 9, 2010
Phase 3 Clinical Study Of A New Cancer Immunotherapy Extends Survival In Patients With Refractory Melanoma..JimBreitfeller
The Cancer Research Institute, a nonprofit organization dedicated to the development of immune system-based treatments for cancer, announced its celebration of a significant new breakthrough in the treatment of melanoma, the deadliest form of skin cancer. The new treatment, a cancer immunotherapy created by Cancer Research Institute Scientific Advisory Council Associate Director James P. Allison, Ph.D., is designed to "take the brakes off the immune system," and is the first treatment ever proven to extend life for patients whose melanomas are unresponsive to existing cancer therapies.
Results from a large, randomized, multicenter phase 3 clinical study, published Saturday in the New England Journal of Medicine, confirm that the new treatment, a monoclonal antibody called ipilimumab, successfully boosts and sustains immune system responses against melanoma tumors in a large percentage of treated patients. The study also shows that the new treatment confers a survival advantage in a significant number of patients, resulting in durable protection against cancer.
According to the study report, 46 percent of patients on the trial who received ipilimumab were still alive at one year compared to 25 percent of patients on the trial who did not receive the new treatment. At two years, 22 to 24 percent of treated patients were still living compared to 14 percent in the study's control arm. The study tested ipilimumab alone, in combination with a vaccine targeting the melanoma tumor antigen peptide gp100, and vaccine alone.
"As an organization that for nearly 60 years has focused on advancing new immune system-based cancer treatments like the monoclonal antibody ipilimumab, the Cancer Research Institute considers this new breakthrough yet another significant success for the field of tumor immunotherapy and further validation that the immune system can be harnessed to treat, control, and prevent cancer," said CRI executive director Jill O'Donnell-Tormey, Ph.D.
In May this year the FDA approved the first therapeutic cancer vaccine, sipuleucel-T (Provenge®) for the treatment of prostate cancer. For the ipilimumab therapy, Bristol-Myers Squibb, the drug's manufacturer, says it expects to file for regulatory approval of its new treatment later this year. If successful, the drug could be the next cancer immunotherapy to receive FDA approval.
T cells (T lymphocytes) are immune cells the play a critical role in the body's attack against tumors. Ipilimumab represents the first in a new class of cancer immunotherapies called T-cell potentiators, which modulate the "stop/go" signals that control T-cell activation. By suppressing these "stop" signals, ipilimumab allows the T-cell response against cancer to proceed unimpeded.
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New RA Treatment Approved - Attn Healthcare Professionals. FDA Approved Treatment. Find Out More. - www.OptionsInRA.com
Ipilimumab specifically blocks CTLA-4, a molecule that inhibits the activity of T cells. Dr. Allison showed in 1995 that CTLA-4 was a negative regulator of T-cell responses, and hypothesized that blocking it could lead to strong tumor rejection. He went on to develop a monoclonal antibody that successfully blocks CTLA-4, and conducted the early mouse studies confirming his hypothesis of anti-CTLA-4-mediated tumor regression.
According to Dr. Allison, T-cell potentiation with ipilimumab may eventually help patients with many different types of cancer live longer. "Studies have shown that the immune system can recognize, target, and attack many different kinds of cancer," Allison said, "and ipilimumab may help to strengthen and sustain that immune response, no matter the type of cancer."
F. Stephen Hodi, M.D., a clinical researcher at the Dana-Farber Cancer Institute and principal investigator on the phase 3 study, said melanoma is just the beginning. "We can explore this new treatment in many other kinds of cancer, as well."
Smaller clinical studies of ipilimumab in other cancer types, including lung and prostate cancers, suggest the treatment has clinical activity, and further clinical research is ongoing to confirm these data.
According to Jedd D. Wolchok, M.D., Ph.D., also an associate director of the Cancer Research Institute Scientific Advisory Council, a CRI clinical investigator, and one of the clinicians involved in the large phase 3 study, there currently are no approved medicines indicated for patients whose melanomas return after primary treatment.
"The study is very significant," Wolchok stated, "as it is the first time ever that a randomized phase 3 study in melanoma has shown a new treatment to provide an overall survival benefit."
The landmark trial has other important implications for the field beyond establishing the effectiveness of this particular cancer immunotherapy. Axel Hoos, M.D., co-chairman of the executive committee of the CRI Cancer Immunotherapy Consortium, a program that seeks to optimize the development of the emerging field of immuno-oncology, and medical lead for ipilimumab at Bristol-Myers Squibb, said ipilimumab investigation represents a significant advance in how clinical studies of cancer immunotherapies are conducted and evaluated.
"The existing paradigm for evaluating the effectiveness of new cancer treatments is informed by experience with chemotherapy," Hoos said. "The chemotherapy paradigm does not entirely account for the biology and unique mechanisms of action of cancer immunotherapy."
To address this issue, the CRI Cancer Immunotherapy Consortium, in collaboration with international partner organizations, immunologists, and clinical oncologists around the world spearheaded the development of a new operating framework for immuno-oncology.
This new framework encompasses a clinical development paradigm that allows clinicians to more effectively investigate immunotherapies in clinical trials. According to Hoos, the ipilimumab trial results contribute to the validation of the new paradigm. "This offers a path forward for the field for more successful development of immunotherapies in the future," Hoos said.
The Cancer Research Institute is currently testing a variety of therapeutic cancer vaccines through its Cancer Vaccine Collaborative (CVC), a joint program with the Ludwig Institute for Cancer Research. Lloyd J. Old, M.D., director of the Cancer Vaccine Collaborative and director of the CRI Scientific Advisory Council, said the emergence of T-cell potentiators like ipilimumab as well as other modulators of immunosuppression has opened a new front for clinical discovery in cancer vaccine research.
"Over the past ten years, the Cancer Vaccine Collaborative has established an unprecedented understanding of the human immune system response to treatment with cancer vaccines," said Old. "There is now considerable evidence that the body recognizes cancer as foreign, but the full force of the immune system to combat cancer is blunted by inherent safeguards that have evolved over time to prevent the immune system from attacking healthy tissue, a condition called autoimmunity that can arise when these safeguard mechanisms fail. Blocking CTLA-4 with ipilimumab removes this constraint and permits more efficient immune control of the tumor."
According to Old, the introduction of ipilimumab and therapies that target other mechanisms involved in immune suppression launches a new era in the development of effective cancer vaccines, offering powerful new tools for overcoming the body's powerful restraints on generating protective cancer immunity.
"Ipilimumab represents a major step in the century old dream of incorporating the immune system in our battle against cancer," said Old, "and learning how to maximize the combined therapeutic effects of ipilimumab with other cancer therapies, including the new targeted therapies, is the immediate challenge."
"Our ultimate goal," said O'Donnell-Tormey, "is to establish highly effective immunotherapies as part of the standard of care in the treatment of cancer. The recent FDA approval of Provenge and the striking data on ipilimumab show that significant progress is being made toward achieving this goal."
"Given these recent advances," said Old, "we can predict that therapies based on immunological principles are poised to revolutionize our understanding and treatment of human cancer. Exploiting the power of the immune system to combat cancer is now clearly within our reach."
About the Cancer Research Institute
The Cancer Research Institute (CRI) is the world's only non-profit organization dedicated exclusively to the support and coordination of scientific and clinical efforts that will lead to the immunological treatment, control, and prevention of cancer. Guided by a world-renowned Scientific Advisory Council that includes four Nobel Prize winners and twenty-nine members of the National Academy of Sciences, CRI supports leading-edge cancer research at top medical centers and universities throughout the world. The Cancer Research Institute is ushering in a new era of scientific progress, hastening the discovery of effective cancer vaccines and other immune-based therapies that are providing new hope to cancer patients.
The Cancer Research Institute has one of the lowest overhead expense ratios among non-profit organizations, with more than 85 percent of its resources going directly to the support of its science, medical, and research programs. CRI meets or exceeds all 20 standards of the Better Business Bureau Wise Giving Alliance, the most comprehensive U.S. charity evaluation service, and according to Charity Navigator exceeds or meets industry standards and performs as well as or better than most cancer charities. CRI has also received an 'A' grade for fiscal disclosure and efficiency from the American Institute of Philanthropy as well as top accolades from other charity watchdog organizations.
Source: Cancer Research Institute
“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
Results from a large, randomized, multicenter phase 3 clinical study, published Saturday in the New England Journal of Medicine, confirm that the new treatment, a monoclonal antibody called ipilimumab, successfully boosts and sustains immune system responses against melanoma tumors in a large percentage of treated patients. The study also shows that the new treatment confers a survival advantage in a significant number of patients, resulting in durable protection against cancer.
According to the study report, 46 percent of patients on the trial who received ipilimumab were still alive at one year compared to 25 percent of patients on the trial who did not receive the new treatment. At two years, 22 to 24 percent of treated patients were still living compared to 14 percent in the study's control arm. The study tested ipilimumab alone, in combination with a vaccine targeting the melanoma tumor antigen peptide gp100, and vaccine alone.
"As an organization that for nearly 60 years has focused on advancing new immune system-based cancer treatments like the monoclonal antibody ipilimumab, the Cancer Research Institute considers this new breakthrough yet another significant success for the field of tumor immunotherapy and further validation that the immune system can be harnessed to treat, control, and prevent cancer," said CRI executive director Jill O'Donnell-Tormey, Ph.D.
In May this year the FDA approved the first therapeutic cancer vaccine, sipuleucel-T (Provenge®) for the treatment of prostate cancer. For the ipilimumab therapy, Bristol-Myers Squibb, the drug's manufacturer, says it expects to file for regulatory approval of its new treatment later this year. If successful, the drug could be the next cancer immunotherapy to receive FDA approval.
T cells (T lymphocytes) are immune cells the play a critical role in the body's attack against tumors. Ipilimumab represents the first in a new class of cancer immunotherapies called T-cell potentiators, which modulate the "stop/go" signals that control T-cell activation. By suppressing these "stop" signals, ipilimumab allows the T-cell response against cancer to proceed unimpeded.
Ads by Google
Cancer Treatment Options - Learn about treatment options available to you. There is hope. - CancerCenter.com/CareThatNeverQuits
Cancer Malpractice - Was your cancer diagnosis delayed? Was your prognosis made worse? - www.delayedcancerdiagnosis.com
New RA Treatment Approved - Attn Healthcare Professionals. FDA Approved Treatment. Find Out More. - www.OptionsInRA.com
Ipilimumab specifically blocks CTLA-4, a molecule that inhibits the activity of T cells. Dr. Allison showed in 1995 that CTLA-4 was a negative regulator of T-cell responses, and hypothesized that blocking it could lead to strong tumor rejection. He went on to develop a monoclonal antibody that successfully blocks CTLA-4, and conducted the early mouse studies confirming his hypothesis of anti-CTLA-4-mediated tumor regression.
According to Dr. Allison, T-cell potentiation with ipilimumab may eventually help patients with many different types of cancer live longer. "Studies have shown that the immune system can recognize, target, and attack many different kinds of cancer," Allison said, "and ipilimumab may help to strengthen and sustain that immune response, no matter the type of cancer."
F. Stephen Hodi, M.D., a clinical researcher at the Dana-Farber Cancer Institute and principal investigator on the phase 3 study, said melanoma is just the beginning. "We can explore this new treatment in many other kinds of cancer, as well."
Smaller clinical studies of ipilimumab in other cancer types, including lung and prostate cancers, suggest the treatment has clinical activity, and further clinical research is ongoing to confirm these data.
According to Jedd D. Wolchok, M.D., Ph.D., also an associate director of the Cancer Research Institute Scientific Advisory Council, a CRI clinical investigator, and one of the clinicians involved in the large phase 3 study, there currently are no approved medicines indicated for patients whose melanomas return after primary treatment.
"The study is very significant," Wolchok stated, "as it is the first time ever that a randomized phase 3 study in melanoma has shown a new treatment to provide an overall survival benefit."
The landmark trial has other important implications for the field beyond establishing the effectiveness of this particular cancer immunotherapy. Axel Hoos, M.D., co-chairman of the executive committee of the CRI Cancer Immunotherapy Consortium, a program that seeks to optimize the development of the emerging field of immuno-oncology, and medical lead for ipilimumab at Bristol-Myers Squibb, said ipilimumab investigation represents a significant advance in how clinical studies of cancer immunotherapies are conducted and evaluated.
"The existing paradigm for evaluating the effectiveness of new cancer treatments is informed by experience with chemotherapy," Hoos said. "The chemotherapy paradigm does not entirely account for the biology and unique mechanisms of action of cancer immunotherapy."
To address this issue, the CRI Cancer Immunotherapy Consortium, in collaboration with international partner organizations, immunologists, and clinical oncologists around the world spearheaded the development of a new operating framework for immuno-oncology.
This new framework encompasses a clinical development paradigm that allows clinicians to more effectively investigate immunotherapies in clinical trials. According to Hoos, the ipilimumab trial results contribute to the validation of the new paradigm. "This offers a path forward for the field for more successful development of immunotherapies in the future," Hoos said.
The Cancer Research Institute is currently testing a variety of therapeutic cancer vaccines through its Cancer Vaccine Collaborative (CVC), a joint program with the Ludwig Institute for Cancer Research. Lloyd J. Old, M.D., director of the Cancer Vaccine Collaborative and director of the CRI Scientific Advisory Council, said the emergence of T-cell potentiators like ipilimumab as well as other modulators of immunosuppression has opened a new front for clinical discovery in cancer vaccine research.
"Over the past ten years, the Cancer Vaccine Collaborative has established an unprecedented understanding of the human immune system response to treatment with cancer vaccines," said Old. "There is now considerable evidence that the body recognizes cancer as foreign, but the full force of the immune system to combat cancer is blunted by inherent safeguards that have evolved over time to prevent the immune system from attacking healthy tissue, a condition called autoimmunity that can arise when these safeguard mechanisms fail. Blocking CTLA-4 with ipilimumab removes this constraint and permits more efficient immune control of the tumor."
According to Old, the introduction of ipilimumab and therapies that target other mechanisms involved in immune suppression launches a new era in the development of effective cancer vaccines, offering powerful new tools for overcoming the body's powerful restraints on generating protective cancer immunity.
"Ipilimumab represents a major step in the century old dream of incorporating the immune system in our battle against cancer," said Old, "and learning how to maximize the combined therapeutic effects of ipilimumab with other cancer therapies, including the new targeted therapies, is the immediate challenge."
"Our ultimate goal," said O'Donnell-Tormey, "is to establish highly effective immunotherapies as part of the standard of care in the treatment of cancer. The recent FDA approval of Provenge and the striking data on ipilimumab show that significant progress is being made toward achieving this goal."
"Given these recent advances," said Old, "we can predict that therapies based on immunological principles are poised to revolutionize our understanding and treatment of human cancer. Exploiting the power of the immune system to combat cancer is now clearly within our reach."
About the Cancer Research Institute
The Cancer Research Institute (CRI) is the world's only non-profit organization dedicated exclusively to the support and coordination of scientific and clinical efforts that will lead to the immunological treatment, control, and prevention of cancer. Guided by a world-renowned Scientific Advisory Council that includes four Nobel Prize winners and twenty-nine members of the National Academy of Sciences, CRI supports leading-edge cancer research at top medical centers and universities throughout the world. The Cancer Research Institute is ushering in a new era of scientific progress, hastening the discovery of effective cancer vaccines and other immune-based therapies that are providing new hope to cancer patients.
The Cancer Research Institute has one of the lowest overhead expense ratios among non-profit organizations, with more than 85 percent of its resources going directly to the support of its science, medical, and research programs. CRI meets or exceeds all 20 standards of the Better Business Bureau Wise Giving Alliance, the most comprehensive U.S. charity evaluation service, and according to Charity Navigator exceeds or meets industry standards and performs as well as or better than most cancer charities. CRI has also received an 'A' grade for fiscal disclosure and efficiency from the American Institute of Philanthropy as well as top accolades from other charity watchdog organizations.
Source: Cancer Research Institute
“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, June 8, 2010
Ipilimumab update Melanoma..Jim Breitfeller
Jim,
First, you should know that you have a great site. I read multiple entries in your blog and found them all both educational and heartfelt. It is so great what you are doing, educating others while offering hope and strength for them and their families during their challenging times. I am so sorry for the loss of your brother and that now you yourself suffer from Melanoma. I have seen first hand the destruction that this fierce disease can do to a person but I have also seen how a great deal of faith and medical miracles can bring hope to the hopeless. That is why I am personally so excited by Ipilimumab, or IPI. My friend Beca was selected for a 'compassionate' study with the IPI between pre and post FDA approval of the drug and actually starts her second round today! We are all hoping this miracle drug can work it's magic on her. You said it best, "The best Melanoma patient is an active participant in his or her treatment" and I could not agree more. You are a perfect example of this.
I think you might be interested in this video. It talks more about Ipilimumab and includes the side effects of possible arthritis etc and the fact that the drug is choosy as to who it will work for, only 20 - 30% of it's patients. However, and I'm sure you will agree, this is still a huge and exciting breakthrough. I hope you see the relevance of this and that you will consider embedding it into Melanoma Missionary. The best of luck to you and your family as you continue this challenging climb. I hope that this email finds you well.
Please let me know if you have any questions,
Haley
Jim's Response
Haley, I believe I know why Ipi only responds in 20-30%. I have been researching this for a while and the missing link is the "Danger Signal". All the pieces of the Melanoma are not there yet, I am closing in on it. I believe we can increase the response rate by combinatorial Therapy with Ipi and IL-2. Dose and scheduling of the drugs play important part of this Orchestration.
If you Look back at some of my posts and research papers, You will see the Light at the end of the tunnel.
Please keep me posted about your friend. Make sure that they (The Oncologist) gets the ALC Absolute Lymphocyte Count before, and during your friends treatment. If the counts rise by a factor of about two, it may be an indication that the Ipilimumab (Anti-CTLA-4 Blockade is working. It would help activate the CD8+ T-cells (CTLs) Cytoxic T Lymphocytes.
Best Regards,
Jimmy B
pp
“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
First, you should know that you have a great site. I read multiple entries in your blog and found them all both educational and heartfelt. It is so great what you are doing, educating others while offering hope and strength for them and their families during their challenging times. I am so sorry for the loss of your brother and that now you yourself suffer from Melanoma. I have seen first hand the destruction that this fierce disease can do to a person but I have also seen how a great deal of faith and medical miracles can bring hope to the hopeless. That is why I am personally so excited by Ipilimumab, or IPI. My friend Beca was selected for a 'compassionate' study with the IPI between pre and post FDA approval of the drug and actually starts her second round today! We are all hoping this miracle drug can work it's magic on her. You said it best, "The best Melanoma patient is an active participant in his or her treatment" and I could not agree more. You are a perfect example of this.
I think you might be interested in this video. It talks more about Ipilimumab and includes the side effects of possible arthritis etc and the fact that the drug is choosy as to who it will work for, only 20 - 30% of it's patients. However, and I'm sure you will agree, this is still a huge and exciting breakthrough. I hope you see the relevance of this and that you will consider embedding it into Melanoma Missionary. The best of luck to you and your family as you continue this challenging climb. I hope that this email finds you well.
Please let me know if you have any questions,
Haley
Jim's Response
Haley, I believe I know why Ipi only responds in 20-30%. I have been researching this for a while and the missing link is the "Danger Signal". All the pieces of the Melanoma are not there yet, I am closing in on it. I believe we can increase the response rate by combinatorial Therapy with Ipi and IL-2. Dose and scheduling of the drugs play important part of this Orchestration.
If you Look back at some of my posts and research papers, You will see the Light at the end of the tunnel.
Please keep me posted about your friend. Make sure that they (The Oncologist) gets the ALC Absolute Lymphocyte Count before, and during your friends treatment. If the counts rise by a factor of about two, it may be an indication that the Ipilimumab (Anti-CTLA-4 Blockade is working. It would help activate the CD8+ T-cells (CTLs) Cytoxic T Lymphocytes.
Best Regards,
Jimmy B
pp
Multisource political news, world news, and entertainment news analysis by Newsy.com
“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, June 7, 2010
Unleashing the Immune System to Destroy Melanoma..Jim Breitfeller
Applying dosing schedules to the clinical protocols of combinatorial therapy, we can optimize the clinical outcome 4-14-2010
The Making of an Immune Response using Anti-CTLA-4 Blockade with Interluekin 2
There is one missing link in all of this. The "DANGER SIGNAL"
How do we generate the Danger Signal so our immune system knows that there are foreign invaders (Melanoma Cancer cells)are present? I have been researching this for quite some time now. I call it the "Missing Link". Bristol Myer Squibb thinks that their Ipilimumab can be used as a monotherapy, but they are mistaken. They want you to believe that their drug is doing all the work but behind the sences there is real Biochemistry taking place. Interluekin-2 is one of the most important players in this Orchestra.
In the next couple of weeks I will elaborate on my theory of the Danger Signal and reveal the pieces of the puzzle that i have discovered in my research.
But for now, let the light shine on Ipilimumab, (anti-CTLA-4 blockade) from Bristol Myer Squibb
“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
Saturday, June 5, 2010
Drug, Ipilimumab boosts survival in major skin cancer study.Melanoma .Jim Breitfeller
Drug boosts survival in major skin cancer study
By MARILYNN MARCHIONE (AP) – 50 minutes ago
Check our my paper called Melanona and the Magic Bullet (Monoclonalantibodies)
Melanona and the Magic Bullet (Monoclonalantibodies)
"Today might be the worst day of your life...but tomorrow could be the best. You just have to get there."
~Unknown~
CHICAGO — Researchers have scored the first big win against melanoma, the deadliest form of skin cancer. An experimental drug significantly improved survival in a major study of people with very advanced disease.
The results, reported Saturday at a cancer conference, left doctors elated.
"We have not had any therapy that has prolonged survival" until now, said Dr. Lynn Schuchter of the Abramson Cancer Center at the University of Pennsylvania, a skin cancer specialist with no role in the new study or ties to the drug's maker.
The drug, ipilimumab, (ip-ee-LIM-uh-mab), works by helping the immune system fight tumors. The federal Food and Drug Administration has pledged a quick review, and doctors think the drug could be available by the end of this year.
"People are going to have a lot of hope and want this drug, and it's not on their doctors' shelves," although some may be able to get it through special programs directly from its maker, Bristol-Myers Squibb Co., Schuchter said.
The study involved 676 people around the world with advanced, inoperable melanoma who had already tried other treatments — a very grim situation. They were given one of three treatments: ipilimumab by itself, with another immune-stimulating treatment, or the immune-stimulating treatment alone.
After two years, 24 percent of those given the drug alone or in combination were alive, versus 14 percent of those given just the immune-stimulating treatment.
Average survival was 10 months with ipilimumab versus just over 6 months for the others, which worked out to a 67 percent improvement in survival for those on the drug, said one of the study's leaders, Dr. Steven O'Day of the Angeles Clinic and Research Institute in Los Angeles.
Doctors hope the drug can provide more benefit if given earlier in the course of the disease and to less sick patients.
Ten percent to 15 percent of patients on ipilimumab had serious side effects related to the drug's actions on the immune system. Most were treatable with high doses of steroids, but 14 deaths were thought to be related to the treatment. That's still far fewer than deaths due to the cancer.
The study was funded by Bristol-Myers and Medarex Inc., a company that co-developed the drug and was bought by Bristol-Myers last year. A spokeswoman said Bristol-Myers has not yet set a price for the drug, but similar treatments for other cancers cost several thousand dollars a month or more.
Results were reported at the American Society of Clinical Oncology's annual conference in Chicago and published online by the New England Journal of Medicine.
Melanoma is the most serious form of skin cancer. Last year in the United States, there were about 68,720 new cases and 8,650 deaths from the disease. Worldwide, more than 50,000 people die of melanoma each year.
___
Online:
Cancer meeting: http://www.asco.org
“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
By MARILYNN MARCHIONE (AP) – 50 minutes ago
Check our my paper called Melanona and the Magic Bullet (Monoclonalantibodies)
Melanona and the Magic Bullet (Monoclonalantibodies)
"Today might be the worst day of your life...but tomorrow could be the best. You just have to get there."
~Unknown~
CHICAGO — Researchers have scored the first big win against melanoma, the deadliest form of skin cancer. An experimental drug significantly improved survival in a major study of people with very advanced disease.
The results, reported Saturday at a cancer conference, left doctors elated.
"We have not had any therapy that has prolonged survival" until now, said Dr. Lynn Schuchter of the Abramson Cancer Center at the University of Pennsylvania, a skin cancer specialist with no role in the new study or ties to the drug's maker.
The drug, ipilimumab, (ip-ee-LIM-uh-mab), works by helping the immune system fight tumors. The federal Food and Drug Administration has pledged a quick review, and doctors think the drug could be available by the end of this year.
"People are going to have a lot of hope and want this drug, and it's not on their doctors' shelves," although some may be able to get it through special programs directly from its maker, Bristol-Myers Squibb Co., Schuchter said.
The study involved 676 people around the world with advanced, inoperable melanoma who had already tried other treatments — a very grim situation. They were given one of three treatments: ipilimumab by itself, with another immune-stimulating treatment, or the immune-stimulating treatment alone.
After two years, 24 percent of those given the drug alone or in combination were alive, versus 14 percent of those given just the immune-stimulating treatment.
Average survival was 10 months with ipilimumab versus just over 6 months for the others, which worked out to a 67 percent improvement in survival for those on the drug, said one of the study's leaders, Dr. Steven O'Day of the Angeles Clinic and Research Institute in Los Angeles.
Doctors hope the drug can provide more benefit if given earlier in the course of the disease and to less sick patients.
Ten percent to 15 percent of patients on ipilimumab had serious side effects related to the drug's actions on the immune system. Most were treatable with high doses of steroids, but 14 deaths were thought to be related to the treatment. That's still far fewer than deaths due to the cancer.
The study was funded by Bristol-Myers and Medarex Inc., a company that co-developed the drug and was bought by Bristol-Myers last year. A spokeswoman said Bristol-Myers has not yet set a price for the drug, but similar treatments for other cancers cost several thousand dollars a month or more.
Results were reported at the American Society of Clinical Oncology's annual conference in Chicago and published online by the New England Journal of Medicine.
Melanoma is the most serious form of skin cancer. Last year in the United States, there were about 68,720 new cases and 8,650 deaths from the disease. Worldwide, more than 50,000 people die of melanoma each year.
___
Online:
Cancer meeting: http://www.asco.org
“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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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.
Jimmy and Dee
Carepage: Jimmybreitfeller
Jimmy Breitfeller
It was he, who showed me How to live and give back. He was wise beyond his years.
Jimmy and Dee
Carepage: Jimmybreitfeller
Jimmy Breitfeller
My Profile as of 2009
- jimmy_B
- 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
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)"
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)
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
"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
Turn off Music before you "Click to Play"
Signs of Melanoma Carcinoma Skin Cancer
Signs of Melanoma Carcinoma Skin Cancer
How Skin Cancer Develops by "About.com : 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)
PingpankJF@UPMC.edu
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
Blog Archive
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2010
(121)
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June
(13)
- New drug can increase life for Melanoma patients.....
- Grapgic Update.. New Pieces to the Melanoma Puzzle...
- CTLA-4 Ligation Blocks CD28-dependent T Cell Activ...
- Master Combination..Melanoma.. Jim Breitfeller
- Pittsburgh Trip (06/28/06) in detail:How my Melano...
- “It is not the strongest of the species that survi...
- Schuchter: Drug Rivals Work Together to Battle Mel...
- Dr. Keith T. Flaherty,reviews a landmark phase III...
- Improved Survival with Ipilimumab in Patients with...
- Phase 3 Clinical Study Of A New Cancer Immunothera...
- Ipilimumab update Melanoma..Jim Breitfeller
- Unleashing the Immune System to Destroy Melanoma.....
- Drug, Ipilimumab boosts survival in major skin can...
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June
(13)
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)
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.