Targeting Tim-1 to Circumvent Immune Tolerance in Prostate Cancer
Revised final rept. 15 Jun 2009-14 Aug 2012
BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
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Early-stage clinical testing raises the possibility that combinatorial approaches that augment tumor antigen-specific immune responses may accomplish significant tumor destruction without the induction of serious autoimmune disease. Accordingly, a rational and combinatorial manipulation of immune evasion pathways and their targets should aid in the development of safer and more effective vaccine strategies and immunotherapies for all stages of prostate cancer. In prostate cancer, a plausible combination that could be targeted towards patients who undergo androgen ablation, a therapeutic modality that is also known to enhance immune responses to prostate TAA, would include a vaccine in conjunction with biologic agents that are known to simultaneously augment antigen presentation by DCs and inhibit immunosuppressive cells such as regulatory T cells Treg or prolong the survival and enhance the vigor of tumor-specific lymphocytes. An example of such agents is the agonist antibody that targets TIM-1, a receptor expressed on lymphocytes and dendritic cells that enhances cytotoxic lymphocyte responses to tumor-associated antigens when used in combination with a vaccine. Here we explore the combination of androgen ablation and anti-TIM1 targeting as a strategy to ameliorate cancer-specific vaccine outcome in a mouse model of prostate cancer.
- Anatomy and Physiology
- Medicine and Medical Research