Challenges and Opportunities Ahead..Melanoma Therapy ..Jim Breitfeller

"A dynamic picture is emerging in which the immune system is far from quiescent in cancer, and tumor cells elaborate a host of countermeasures to evade immune destruction. In essence, these are two systems which co-evolve over time. Clinical outcome is ultimately a balance between the proliferation of tumor cells and the immune response which attempts to control these cells. Various treatments may perturb these two systems in different ways - in good clinical outcomes, the immune response ultimately dominates, while in poor outcomes, tumor cells dominate.

It is becoming clear that the challenge in tumor immunotherapy lies not only in lack of tumor recognition, but also ineffectivity of the immune response that develops. While efforts to elicit tumor-specific T cells directly in patients via vaccination may overcome potential mechanisms of immune evasion by tumors cells, current immunotherapeutic strategies do not address their potential immunomodulatory mechanisms.

Understanding the molecular mechanisms which underlie T cell dysfunction in cancer will be important to devise novel adjunct strategies to enhance or modulate T cell responses after tumor-specific T cells have been elicited. It will likely take a multi-faceted approach acting at several steps along the T cell activation and effector activity pathway to finally achieve success in cancer immunotherapy."


The Laboratory of Peter P. Lee, MD at Stanford University

This multi-faceted approach acting at several steps along the T cell activation and effector activity pathway is what I call Combinatorial Therapy.

We first start at obtaining the Antigen to be presented on the Antigen Presenting Cell. Then once we think we got it, we need to proceed to the Activation step. Ipilimumab (Anti-CTLA-4 Blockade) helps to keep the activation in the on position. It also has a dual role, in keep the Treg's surpressive function out of play in the Tumor 's microenvirioment.
Interleukin -2 is the final step to complete response. It is the growth factor for the CTL's, which help maintain functionality and survival of the Cytotoxic T Lymphocytes (CTL's).






Take Care,

Jimmy B