Exploiting the Innate Antitumor Activity of Human Gamma-Delta T-Cells for the Treatment of Prostate Cancer

摘要

We initially identified and characterized a CD2-mediated, interleukin (IL)-12-dependent signaling pathway which inhibits apoptosis in mitogen-stimulated human gamma-delta-T cells. We have since exploited this pathway to develop the methodologies allowing the large-scale ex vivo expansion of viable apoptosis-resistant gamma-delta-T cells. We have shown that apoptosis- resistant human gamma-delta-T cells retain significant innate, major histocompatibility complex (MHC)-unrestricted cytotoxicity against human prostate cancer cell lines. Purpose and scope: The aims of this project are, (1) to more precisely characterize the extent and breadth of the antitumor cytotoxicity mediated by apoptosis-resistant human gamma-delta-T cells against human prostate cancer cells; (2) to define the general mechanisms involved in the recognition and lysis of sensitive prostate cancer cells by apoptosis- resistant gamma-delta-T cells; and (3) to determine the extent to which apoptosis-resistant gamma-delta T cells can regulate the growth and metastasis of prostate cancer cells in vivo.