Tumors as elusive targets of T-cell-based Active Immunotherapy..Melanoma..Jim Breitfeller

Dr. Herlyn, I been researching my successful Melanoma treatment and came across a research paper of yours “Tumors as elusive targets of T-cell-based active immunotherapy”. It postulates the mechanism underlying is the Antigen-Specific T-cell base immunotherapy can result in a complete response if activated appropriately. I believe that you diagram was right on target. My therapy was three clinical trials that followed your proposed mechanism. I did DTIC + PaTrin-2 to shed the right antigenic protein. Then I used Anti-CTLA-4 blockage to activate CD4+ T-cells and suppress the Tregs. IL-2 HD was added to help differentiate the T-cells and maintain there function and survival. Timing and dosing concentration played a major factor in breaking the balance of the tumor’s microenvironment. During my therapy I did get an inflammation response leading to a complete response.



Attached is a draft of what transpired and the dosing and timing. I believe this information might be very helpful in your research.
(See My Shared files)



"Melanoma and the Magic Bullet (monoclonal antibodies"



Fig. 2. Postulated mechanism underlying tumor antigen (TA)-specific T-cell-based immunotherapy and effect on target antigen expression. Localization of TA-specific
T cells at a tumor site appears to be necessary but not sufficient for tumor elimination [38,39]. If no response occurs, the interaction between T cell and tumor cell is
probably not sufficient (or sustained) to start or maintain an inflammatory process. If the treatment induces an adaptive response of a quality and/or intensity that exceeds
a certain ‘threshold’, then direct interaction of T cells with antigen-expressing (red circles) tumor cells leads to their destruction, as well as to the production of proinflammatory
and pro-apoptotic cytokines that induce secondary activation of adaptive and innate immune effectors capable of clearing tumor cells that have lost antigen
expression (white circles). If the tumor-cell destruction is not complete, the proliferation of remaining cells leads to recurrence. In those cases, the recurring tumors have
lost the surface expression of the epitope relevant to the vaccination [66,67]. Abbreviations: CR, complete response; PR, partial response; X, cells killed by the therapy.

Source:http://www.wistar.org/Herlyn/Pub%20PDFs/Marincola2003pdf.pdf

Tumors as elusive targets of
T-cell-based active immunotherapy

As you can see, the maxium Antibody level occurs on day 20. My Inflamed response occurred on day 15. This all fits together.






Take Care,

Jimmy B