Exploiting the Innate Antitumor Activity of Human Gamma-Delta T-Cells for the Treatment of Prostate Cancer
Annual rept. 1 Apr 2004-31 Mar 2005
ALABAMA UNIV IN BIRMINGHAM
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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.
- Anatomy and Physiology
- Medicine and Medical Research