Exploiting the Innate Antitumor Activity of Human γδ-TCells for the Treatment of Prostate Cancer

Purpose: We have previously identified a CD2 mediated, interleukin-12 dependent signalingpathway that inhibits activation induced cell death in mitogen stimulated human -T cells,permitting the large-scale expansion of these cells. Herein we report the innate antitumoractivity of expanded human V 9V 2 -T cells against human prostate cancer cells.Materials and Methods: Apoptosis resistant human -T cells were expanded in vitro fromcultured human peripheral blood mononuclear cells and then enriched to high purity by immu-nomagnetic separation. In vitro cytotoxicity of expanded -T cells was measured against humanprostate cancer cell lines using standard cytotoxicity assays.Results: -T cells derived from various donors consistently showed lytic activity against theprostate cancer cell lines DU-145 and PC-3 but not LNCaP. mAbs against V 9 or V 2 T-cellreceptor chains as well as mAb against intercellular adhesion molecule-1 (ICAM-1) or CD18, thesubunit of ICAM-1 counter receptors, blocked -T cell mediated killing of prostate cancer cells.-T cells lysed prostate cancer cell lines largely through the perforin/granzyme pathway.Conclusions: Ex vivo, expanded human V 9V 2 -T cells are able innately to recognize andkill certain human prostate tumor cell lines in vitro. The recognition and killing of prostatecancer cells occurs in a -T-cell receptor dependent manner and it also appears to involveinteractions between ICAM-1 and CD18. Because apoptosis resistant human V 9V 2 -T cellscan readily be expanded to large numbers (clinical scale), these findings must be considered inthe context of developing adoptive immunotherapy strategies to exploit -T cell innate immuneresponses to prostate cancer.