Enhancing Anti-Prostate Cancer Immunity Through OX40 Engagement

摘要

The goal of the proposed studies is to extend our OX40-specific anti- tumor responses to prostate tumor models by using a protein found on the surface of the T helper subset of leukocytes (OX40). Anti-OX40 delivered into animals with ongoing immune responses are able to clear the tumors and pathogens quicker following the acute immune response and also are left with a greater amount of immunologic memory . The greater number of memory T cells patients have that recognize these tumors, increases their chance to fight off subsequent metastatic disease. We have found that prostate cancer patients treated with androgen ablation have a large influx of leukocytes into their prostate gland. These cells enter the prostate gland to recognize and destroy tumor cells. Leukocytes that invade the prostate gland after androgen ablation are OX40+. Therefore, we hypothesize that androgen ablation followed by anti- OX40 treatment will enhance anti-tumor immunity in these patients and we propose to exploit our discovery in prostate cancer mouse model. Fine-tuning our approach to gain preclinical data will help us to understand the most efficient way to augment anti-prostate cancer immunity in prostate cancer patients for future clinical trials.