Giving Thanks… Five Years Later..Melanoma..Jim Breitfeller

Giving Thanks… Five Years Later

Back in July of 2005 I was diagnosed with Melanoma Cancer. It has turned my life inside out and upside down. Here is a note that I sent to my colleagues at Eastman Kodak.


Dear Friends and Family,


I wanted to take a moment to let you know that I’ll be leaving my position at Eastman Kodak Company as of March 9, 2007. I will be starting a new phase of my life trying to win this battle of cancer. My short term disability ends and the long term starts.


I have enjoyed my 25 years there and I appreciate having had the opportunity to work with each and every one of you. Thank you for the support, guidance, and encouragement you have provided me during my time at Kodak. Even though I will miss my colleagues and the company, I am looking forward to this new challenge and to starting a new phase of my life. Even though the paths are many, I must go down each one to find the “Yellow Brick Road.” With your support and encouragement we can beat this disease together.

Please keep in touch,


Jimmy B


It has been five years now and I believe I accomplished what I had set out to do, that was to beat this disease melanoma. With the help of family, carepage friends and researchers, oncologists, we have come a long way. I have spent most of my waking hours researching and helping fellow melanoma comrades traverse the canyons of this disease. Along the way I have met and lost so many friends to this disease and only wish that they could be here today to celebrate with me.



Without you, I would not have been so focused on finding a cure. So today , I just want to say thanks for everything. Thanks for keeping me on the right path and believing in me. We are making great inroads in understanding the immune system and how it can be trained to eradicate Cancer. We are in the emergence of the renaissance (A rebirth) of Immunology and Combinatorial Therapy. I believe whole heartedly that we will see a Cure for cancer in my lifetime.

We must keep on persevering to obtain that goal.


Jimmy B


“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

 

Macrophage Activation… The Missing Link to Activation an immune response to Melanoma..Jim Breitfeller

"The development of Th1 cells producing high levels of IFN-gamma could not be induced with dendritic cells alone but required the addition of appropriately activated macrophages." Et al A. O'Gara March 23, 1993 "Dendritic cells and macrophages are required for Th1 development of CD4+ T cells from αβ TCR transgenic mice: IL-12 substitution f.or macrophages to stimulate IFN-γ production is IFN-γ-dependent"
Local IL-12 therapy stimulates Th cells to secrete Th1 cytokines. Exogenous IL-12 application creates an environment rich in IL-12 around the cancer site. In such a local environment, newly activated Th cells, responding to the presence of cancer, exit the blood and are influenced to become Th1 cells and secrete more Th1 cytokines and activate macrophages and NK cells. Activated macrophages will produce more IL-12 and via positive feedback, cell-mediated immunity can be promoted to battle the cancer thereby leading to the prevention of reoccurrence. As you can see, the activated macrophage secretes IL-12, IL-1a, IL-1b, and IL-6 along with a Chemoattractant, IP-10. Without macrophage activation, the immune response does not take place and the patient will relapse.(see graphic below)

With IL-1b and IL-6 missing, the T-Regulatory Cells (Tregs) rule the Tumor's Microenviroment. IL-6 controls Th17 immunity by inhibiting the conversion of naive CD4+ T cells into Foxp3+ regulatory T cells. IL-1β–Mediated Signals Preferentially Drive Conversion of Regulatory T Cells but Not Conventional T Cells into IL-17–Producing Cells (Danger Signal).So if the IL-1b signaling is missing,conversion of the Tregs never take place along with no Danger Signals.

Dr. Steven Rosenberg is using engineered T-cells that secrete IL-12 to stimulate Th cells to secrete Th1 cytokines. This sets in motion the positive feed back loop needed to initiate an immune response. His therapy is show great promise. “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

ESMO 2010: Tumor immunology and combined immunotherapies - Prof Ignacio Melero - University of Navarra, Pamplona, Spain

ESMO 2010: Tumour immunology and combined immunotherapies - Prof Ignacio Melero - University of Navarra, Pamplona, Spain

“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

Interview with Dr. Jim Allison. ..The making of Yervoy..Melanoma..Jim Breitfeller

To Cure cancer, your immune system  must make memory cells that can distingush Melanoma cancer when and if you relapse. This done in at initial stage of T-cell Differentation and propagation. You must have the right Melieu (An environment or a setting) in place. This can be done with Systematic Combinatorial Therapy.

“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

Thinking outside the Box for the Elderly Melanoma Cancer Patients..Jim Breitfeller

Immunotherapy and Cancer - KTVN Channel 2 - Reno Tahoe News Weather, Video -
New rules of engagement for older patients The body’s immune system does weaken with age, but it also changes, and that changes the rules for fighting disease within the body. Dr. Curiel’s group started by examining an immune therapy that they previously had shown to work in younger hosts, including cancer patients. It’s designed to eliminate regulatory T cells (called Tregs), which are cells that turn off immune responses, allowing cancer to progress. Tregs increase in cancer. In young hosts, the drug turns off Treg activity, allowing the immune system to function better. In older hosts, even though the drug turns off the Tregs, it has no clinical benefit. Dr. Curiel asked the question why, and in this paper his team explains the answer. In older mice, when the drug turned off the Tregs, the researchers found that another type of immune suppressor cell (a myeloid-derived suppressor cell or MDSC) exploded in number to take the Tregs’ place, hampering clinical efficacy. That did not happen in young mice. The team added a second drug that targets the MDSC, and found that with those tools to help immunity, the older hosts can combat cancer just as well as the younger hosts. Adding the second drug afforded no clinical benefit to young hosts, as their MDSC numbers had not increased. “We’ve shown that an aged immune system can combat cancer just as well as a young one if you remove the impediments to successful immunity, which are different than those in younger hosts,” Dr. Curiel said. “We’ve shown that if you test all your immune therapy just in young mice and young people, you’ll never learn how it works in older patients — the ones most at risk for cancer. You might conclude that drugs don’t work in aged hosts, when they do. But they have to be combined with some help.” Human trials on the horizon The next step is to test these concepts in an immune therapy clinical trial for elderly patients, which the research team plans to do, Dr. Curiel said. The drug that is added is anti–Gr-1 antibody and would have to get approval from the FDA, meaning Clinical Trial. With that said, What if we added 5-Fluorouracil to immunotherapy like Yervoy and or Anti-PD1. 5FU immunogenic effects are primarily attributable to MDSC depletion. 5-Fluorouracil selectively kills Tumor-Associated Myeloid-Derived Suppressor Cells Resulting in Enhanced T Cell–Dependent Antitumor Immunity. This would be the one, two punch for elderly cancer patients. Let's Think outside the box. Myeloid-derived suppressor cells (MDSC) have been identified as a population of immature myeloid cells with the ability to suppress T-cell activation in humans and mice. These cells accumulate in the blood, lymph nodes, bone marrow, and at tumor sites in many human cancers and animal tumor models, and inhibit both adaptive and innate immunit. They notably have the capacity to inhibit CD8+ T cell antigen-specific reactivity by different mechanisms, mainly through their capacities to produce nitric oxide and radical oxygen species.




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

I finally have some good news to report!..Julie..Melanoma ..Jim Breitfeller

I finally have some good news to report!

Quick review: Dx Feb 2011 WLE SNLB positive microscopic 1 node. Complete rt groin dissection- rest of nodes negative. Did high dose interferon May 2011, 1 high dose injection then stopped. Surgery July 1 for recurrence at bottom of lymph node scar. Did 4 rounds biochemo- July , august, sep, oct. Recurrence again in same area surgery end November. Started Yervoy end dec had 2 rounds then did radiation to right leg 20 treatments. Finished 4th Yervoy on 2/15/2012.

First PET/CT post Yervoy 02/28/2012 showed "Extensive progression of malignant disease with development of multiple, hepatic, osseous and pulmonary metastatic lesions."

Labs were also awful- LDH got up to 414. Liver enzymes markedly elevated alk phosphatase 374, ast 499, alt 1106.

Labs yesterday-LDH 152 normal!!. Liver enzymes alk phosphotase 142, ast 81, alt, 111 these are still a little high, but markedly improved.
PET/CT: " Very pronounced improvement in metastatic disease. Most of the pulmonary modules noted previously are no longer visible. A few small punctate nodules remain. Only one has identifiable activity on PET portion with < 1 SUV. It measures only a few millimeters. Hepatic metastatic disease has significantly improved. Very significant improvement in skeletal metastatic disease. Many lesions are no longer visible."

Hallelujah!!!!!!!!
Can't stop doing the happy dance.

I'm praying for all to see some improvement in their disease and even a cure.
Hope this post gives some hope to others. I really wonder if the biochemo with IL2 followed by Yervoy along with some radiation is the key to my body finally getting the message.

Julie in Las Vegas

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Julie, Congrats!!!!!

"I really wonder if the biochemo with IL2 followed by Yervoy along with some radiation is the key to my body finally getting the message .".."

You are right on target. The biochem with IL-2 primed your Immune system, while Yervoy deactivated the T-Regs cell suppression of your T-cells. Radiation added the tumor cell debris that is needed to be presented on the Dendritic Cells which are acting as the Antigen Presenting Cells (APCs). The process can be presented in this Diagram.




Remember the this blog. It will lead to a CURE!!! Combinatorial Therapy


“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