Friday, February 10, 2012

Breaking Tolerance to Invoke an Immune Response to Cancer (Melanoma)..Jim Breitfeller

This post has been in the works for five years. It is with my tenacity and help from researchers around the world I am able to present this paper. It is still in draft form but I thought was important enough to just get it out there. It may be to technical for the average person/patient but, it is well worth downloading and presenting to your oncologist and or medical team.

The gist of the paper is we have responders and non-responders to therapy. WHY?? with the help of Four on the most influential reseachers in the Melanoma field, Dr. Craig Slingluff, Dr. Thomas Gajewski, Dr.Kingston Mills, Dr. Jim Allison and others, I was able to put some puzzle pieces together to tell a story. A story that may just save your life

In short, the non-responders may be/are missing the "Danger Signals" inflammatory Cytokines. Why, because their tumors are most likely harboring M2 phenotype macrophages (TAMs) Tumor assisted Macrophages.

But these TAMs have plasticity. This means they can change phenotype based on their miroenviroment. With some coaxing they can be change into M1 macrophages which in turn activate the T-cells. This means the patient needs to have therapies that promote M1 and Th1 cells. Well both Dr. Allison and Dr. Mills have discovered ways to do just that.

Please take some time to download and read this historic paper. It just may be the game changer for cancer.

Breaking Tolerance to Invoke an Immune Response to Cancer (Melanoma

I am going end with four slides.

“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, February 1, 2012

“I have your results”..Melanoma..Jim Breitfeller

Tuesday, Jan 31, 2012 3:00 PM 17:47:41 EST

“I have your results”

Mary Elizabeth Williams is a staff writer for Salon

Three months into a draining clinical trial, the doctor called with news. Was it working -- or not?
I had just settled into a chair for my regular Tuesday night cancer support group when I got the call. An unfamiliar number. A split second of wondering whether or not to answer. And then my doctor, calling from his own phone to say, “I have your results.”

People with metastatic, Stage 4 melanoma rarely get happy endings. They usually just get endings. The odds of surviving five years once the cancer has spread into your lungs and bloodstream are generally ballparked at around 10 percent. So when I entered a Phase I immunotherapy clinical trial in October, I knew the whole enterprise had the pungent aroma of Last Ditch. My doctors said brightly that my relative youth and good health made me “an ideal candidate.” They said that the drug combination I’d be on – the newly approved Ipilimumab and the experimental, sexily named MDX-1106 – were highly “promising.” Because it was a trial, Bristol-Myers Squibb would essentially foot the bill. They had also just told me that the malignant cancer I had surgery for in 2010 had broken off; there was now a tumor in my lung and another one under the flesh of my back. In the stark absence of other options, I signed a 27-page consent form alerting me to potential side effects from diarrhea to hepatitis and even death. And with that, I started on a protocol that I hoped wouldn’t kill me before the cancer did.
Every three weeks, I spend a day on the fourth floor at Memorial Sloan-Kettering, hooked up to an IV as strange new drugs drip into my system. Every week, I am monitored and quizzed and examined and have truly ludicrous amounts of blood drawn. The external effects of the regimen presented themselves early on – crushing exhaustion, an itchy rash, dizzy spells – but I would have to wait three months, until January, to learn whether the drug combo was doing any real work on my cancer. The fact that the lump on my back subsided after the very first treatment was encouraging enough to get my doctor enthusing, but having been declared “cancer free” once before, I knew to temper optimism with caution. Especially because these are uncharted waters.

Immunotherapy, my doctor says, is like religion. “For years,” he tells me, “we just had to go on faith.” It differs radically from chemo in that it coaxes your body’s own defenses to attack disease – and then, astonishingly, to continue defending the body after treatment has ended. It’s still considered a new frontier in cancer care, and at first glance, it’s easy to see why. Its main forerunner is Interleukin-2, an immune-system treatment for patients with metastatic cancer that is infrequently used and only sporadically effective. And one of the immunotherapy drugs I’m on, Ipilimumab, won FDA approval last year with a mere 30 percent success rate.
Yet the way we treat – and try to head off – cancer is changing radically. Look no further than the rise of the vaccine Gardasil. Since its approval in 2006, it has been routinely given to girls to help ward off HPV, which can cause cervical cancer. And just last week, the Roswell Park Cancer Institute in Buffalo launched a Phase 1 clinical trial for a vaccine researchers say “harnesses the power of the body’s immune system to kill cancer cells.” Imagine a world in which preventing and treating cancer didn’t automatically mean harsh protocols like chemo, radiation or interferon. Imagine something that might someday be as simple as getting a shot. It’s coming. Because as my clinical trial nurse puts it, “It’s the immune system, stupid.”
That dramatic day, however, is still a long way off. In the meantime, if the other 10 people doing this trial at MSKCC are anything like me, they’ve been dealing with scarred veins, side effects and nagging uncertainty. Science may be moving at a breathtaking clip, but when you’ve got a cancer that often kills within a year, it simply may not be moving quickly enough for all of us.
That’s why when my doctor said he had my results, I wasn’t sure I wanted to know. I had been at MSKCC just that morning, guzzling sickly sweet, room-temperature liquid and holding my breath inside the CT scan machine. After three months of infusions, I’d now know whether that spot in my lung was growing or shrinking, whether my cancer was accelerating or diminishing. That night, as I stood in the hall outside my support group, I held my breath again. And then my doctor told me, “I have good news.”

“The tumor in your lungs is gone,” he continued, “and the one on your back has receded completely.” I don’t know a lot of fancy medical jargon, but I do know that “good news,” “gone” and “receded completely” are, for a person with distant metastases, downright extraordinary.
Two days later, I was back at Sloan-Kettering, awaiting my next infusion. “I know you can’t reveal much,” I’d asked, “but can you say anything about how the other people in the trial are doing?” I may be thriving, but if it turned out other patients were dropping like flies, I’d hold off on popping a bottle of Dom.
“We had two other patients who had scans this week,” the doctor said. “Both of their tumors have shrunk significantly. But you’re at 100 percent, so that makes you our valedictorian.” And while it’s nice to be valedictorian, what it really means to a team of researchers — and Bristol-Myers Squibb — is that I am solid results.
This isn’t a happy ending. People with Stage 4 cancer don’t really get those. This isn’t even an ending. I’m still only halfway through a trial that is kicking my ass. After I complete it in March, I will be on maintenance treatment every three months for the next two years. I will have skin checks and MRIs and scans for the rest of my life. I live with the reality that melanoma, as I have already learned firsthand, makes more comebacks than Cher. And nobody really knows for sure what the long-term effects of my treatment are, because nobody’s ever done this particular course before. I’m hoping they include super strength and sexual charisma, but liver damage seems likelier.

Yet right now, I have hope that the middle-aged woman in Treatment Suite 26, the one whose elderly father sits by her side as they watch “Dr. Phil” together, is getting better. That the tall, 20-something guy in the Superman T-shirt, a genial fellow who tells me the cancer has already come back twice before, is too. And it’s a humbling and fantastic thing to consider that, someday, because of what the sick and the healers are doing on the fourth floor, you might get to survive, too.

When I went in for my last treatment, my doctor asked if I wanted to see my scans. You bet I did. He sidled over to a monitor in the corner of the exam room and brought up an image dated Oct. 6, 2011. “This is your lung,” he said. “See that there? That blob? That’s the tumor.” Then he brought up another image right next to it. “This is you now.” It looked just the other one, but with one significant difference. No blob. He did the same for the picture of my back. “Here’s the cancer,” he said. There was a green arrow pointing to it, a flag that some technician added three months ago, a little signpost of malignancy. “And this,” he said, double-clicking on a different picture, “is you now. Nothing.” Nothing has never looked so beautiful.

“Wow,” I replied. “That’s amazing.”
“Yeah, it is,” he said, beaming. “It’s more fun when it works.” I looked at the monitor and smiled too. Within those weird, abstract images I could see so much, so clearly. I could see sunsets and birthday parties; I could see snowmen and sand castles. And I thought, yup, it’s the best fun ever. It’s even better than a happy ending. It’s a future.

Immunotherapy + Cancer Vaccines will be the future.

In my next post I will show you how we can beat cancer (Melanoma) with combinational therapy. This is so new that your Oncologists don't even know about. It is the culmination of the last 5 years of my my search for a cure.

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”
~Charles Darwin~
Take Care,
Jimmy B

Greetings to One and All

This Blog is dedicated My Brother Kenny B. who passed away in the late 1970's with Cancer before the Internet.

It was he, who showed me How to live and give back. He was wise beyond his years.

Kenny B

Jimmy and Dee

Carepage: Jimmybreitfeller
Jimmy Breitfeller

My Profile as of 2009

My photo
Last July (2005)I was riding my bicycle to work at the Eastman Kodak Research Labs about 3 miles from home. I was wearing a knapsack to carry my things to and from the labs. I started noticing an ache on my back. So I decide to go to the dermatologist. To make the long story short, it was cancer. I knew from my research that I would be needing adjuvant therapy. So I started communicating with Sloan Kettering, University of Pittsburgh Cancer Center, and a couple of others including the Wilmot Cancer Center at Strong. I realized that by telling my story, I might help someone else out there in a similar situation. So to all who are linked by diagnosis or by relation to someone with melanoma, I wish you well. Stay positive, read as much as you can (information helps to eliminate the fear associated with the unknown), and live for today, as no one can predict what tomorrow may bring. Jimmy B. posted 12/15/08


The information contained within this Blog is not meant to replace the examination or advice of your Oncologist or Medical Team. The educational material that is covered here or Linked to, does not cover every detail of each disorder discussed.

Only your physician/Oncologist can make medical decisions and treatment plans that are appropriate for you. But, An Educated Consumer is a Smart consumer.

As Dr. Casey Culberson Said:

"The BEST melanoma patient is an ACTIVE PARTICIPANT in his or her treatment

Melanoma and the “Magic Bullet” (Monoclonal Antibodies)

Just to let you know I posted the first draft of the Melanoma and the “Magic Bullet” (Monoclonal Antibodies). on Melanoma Missionary In the Shared File Section. you can download it for 19.95 (Only kidding) it is Free for the taking.

It is 33 pages long and may help you in your quest for the Yellow Brick Broad. Just to let you know it is only the first draft. Revisions are sure to come. I wanted to get it to the people that need it the most, the Melanoma Patients.


So, where does Interluekin-2 (IL-2) come into play? According to Byung-Scok et al and recent reports, IL-2 is not needed for developmental CD4+ CD25+ Treg cells in the thymus but does play an important role in the maintenance and function in the peripheral.18 Peripheral is defines as secondary system outside the bone marrow and thymus. It entails the site of antigen, immune system interaction. IL-2 is required for the peripheral generation of Tregs based Abbas’s and colleagues research.19

IL-2 prevents the spontaneous apoptosis of the CD4+ CD25+ Treg cells. It has been reported that patients with multiple advance-stage tumors have elevated levels of Tregs within the tumor microenviroment.20 Interluekin-2 is the survival factor for CD4+ CD25+ Treg cells.21 If the addition of IL-2 is on or before the maximum propagation of the CD4+ T cells, the Tregs population can increase 5-fold in a 96 hour period based on certain growth mediums.

By controlling the addition of the endogenous IL-2, one has a knob to turn and can lead to the control of the expansion of the Tregs. When you combined this control with the anti-CTLA-4 blockage, you can shift the balance of the immune response.

Now here is the catch. The maintenance and function of the CD8+ T-cells require CD4+ cells which secrete IL-2. So we don’t want to deplete the CD4+ cells, we want to control the expansion of the Tregs which are a subset of the CD4+ cells. It has been postulated by some researchers that the Anti-CTLA-4 blockage also suppresses the Treg function in a different mechanism. By using IL-2 as the rate limiting factor, we can suppress the CD4+ CD25+ Treg cell expansion by controlling the concentration and timing of the Inerluekin-2 at the tumor microenvironment.

The Interluekin-2 plays another role in this Melanoma Maze. In a study by Janas et al, Il-2 increases the expressions of the perforin and granzyme A, B and C genes in the CD8+ T-cells. This increase expression causes the CD8+ T-cells to mature into Cytoxic T Lymphocytes (CTLs). The exogenous IL-2 is required for the granzyme proteins. As stated previously, CTLs have cytoplasmic granules that contain the proteins perforin and granzymes. A dozen or more perforin molecules insert themselves into the plasma membrane of target cells forming a pore that enables granzymes to enter the cell. Once in the tumor cell, these enzymes are able to breakup (lyse) the cell and destroy it. This is the beginning of the end for the cancer cells. The tumors begin to shrink and the rest is history,

On the other hand, prolong therapy with Il-2 can result in causing apoptotic death of the tumor- specific CD8+ T-cells.23

Clearly in a clinical setting, timing, dose, and exposure to these drugs play a major roll in the immunotherapy, and can have dramatic effects on the outcome.

All it takes is that one magic bullet to start the immune reaction..

Melanoma And The Magic Bullet (Monoclonal Antibodies)

Public Service Announcement

A call for Melanoma Patients by Dr. Steven A Rosenberg

"We continue to see a high rate of clinical responses in our cell transfer immunotherapy treatments for patients with metastatic melanoma", Dr. Rosenberg said.

"We are actively seeking patients for these trials and any note of that on a patient-directed web site would be appreciated."

If you would like to apply for his trials, here is the website and information.

Dr. Rosenberg's information

Dr. Rosenberg's Clinical Trials

For the Warriors

The Melanoma Research Alliance has partnered with Bruce Springsteen, the E Street Band, and the Federici family to alleviate suffering and death from melanoma. Please view Bruce Springsteen’s public service announcement inspired by Danny Federici. Danny was the E Street Band’s organist and keyboard player. He died on April 17, 2008 at Memorial Sloan-Kettering Cancer Center in New York City after a three year battle with melanoma.

Source Fastcures blog

Join the Relay for Life!!!


Dear Family and Friends,

I’ve decided to take a stand and fight back against cancer by participating in the American Cancer Society Relay For Life® event right here in my community! Please support me in this important cause by making a secure, tax-deductible donation online using the link below.

To donate on line now, click here to visit my personal page.
Jimmy B AKA Melanoma_Missionary

Relay For Life® is a life-changing event that brings together more than 3.5 million people worldwide to:

CELEBRATE the lives of those who have battled cancer. The strength of survivors inspires others to continue to fight.

REMEMBER loved ones lost to the disease. At Relay, people who have walked alongside people battling cancer can grieve and find healing.

FIGHT BACK. We Relay because we have been touched by cancer and desperately want to put an end to the disease.

Whatever you can give will help - it all adds up! I greatly appreciate your support and will keep you posted on my progress.

Keep the Fire Burning!!!



Jimmy Breitfeller
Turn off Music before you "Click to Play"
Signs of Melanoma Carcinoma Skin Cancer

How Skin Cancer Develops by " : Dermatology"

Call for Patients with Unresectable Liver Metastases Due to Melanoma

Delcath Systems Granted Orphan-Drug Designations for Cutaneous and Ocular Melanoma

Delcath is actively enrolling patients in a Phase III clinical trial testing its proprietary drug delivery system, known as Percutaneous Hepatic Perfusion (“PHP”), with melphalan for the treatment of ocular and cutaneous melanoma metastatic to the liver.

This NCI-led trial is enrolling patients at leading cancer centers throughout the United States. Commenting on these orphan-drug designations, Richard L. Taney, President and CEO of Delcath, stated, “These favorable designations are important steps in our efforts to secure Delcath’s commercial position upon conclusion of our pivotal Phase III trial for metastatic melanoma. We remain steadfast in our commitment to become the leader in the regional treatment of liver cancers and we continue to enroll patients in this study, and advance our technology and the promise that it offers to patients with these deadly forms of melanoma and other cancers of the liver, all with limited treatment options.”

Orphan drug designation, when granted by the FDA’s Office of Orphan Products Development, allows for up to seven years of market exclusivity upon FDA approval, as well as clinical study incentives, study design assistance, waivers of certain FDA user fees, and potential tax credits.

Current Trial Centers

Phase I Study of Hepatic Arterial Melphalan Infusion and Hepatic Venous Hemofiltration Using
Percutaneously Placed Catheters in Patients With Unresectable Hepatic Malignancies

James F. Pingpank, Jr., MD, FACS
Associate Professor of Surgery
Division of Surgical Oncology
Suite 406, UPMC Cancer Pavillion
5150 Centre Avenue
Pittsburgh, PA 15232
412-692-2852 (Office)
412-692-2520 (Fax)

Blog Archive

Call For Melanoma Patients!!!!

Call For Melanoma Patients!!!!

Dr. Rosenberg Has a New Clinical Trial.

Our latest treatment has a 72% objective response rate with 36% complete responses.

We are currently recruiting patients for our latest trial.

Is there some way to post this “Call for Patients” on the web site?

Steve Rosenberg

Dr. Rosenberg's Clinical Trials

(For a copy of the research paper.. see My Shared files)

The news headlines shown above for Melanoma / Skin Cancer are provided courtesy of Medical News Today.