Journal
IMMUNOLOGIC RESEARCH
Volume 26, Issue 1-3, Pages 207-221Publisher
HUMANA PRESS INC
DOI: 10.1385/IR:26:1-3:207
Keywords
gamma delta-T cells; cellular immunotherapy; experimental bone marrow transplantation
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Funding
- NCI NIH HHS [R01CA092174] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R01CA092174] Funding Source: NIH RePORTER
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Human gammadelta-T cells are capable of mediating both innate antitumor and antiviral activity, functions that theoretically might be exploitable in the treatment of a variety of malignant or infectious diseases. Nonetheless, experimental therapies incorporating the adoptive transfer of human gammadelta-T cells have remained unfeasible to date owing largely to the difficulty of isolating or expanding sufficient numbers of gammadelta-T cells. It is in this context that recent discoveries from our laboratory are presented. By identifying specific signaling pathways that selectively inhibit activation-induced apoptosis in apoptosis-prone gammadelta-T cells, we have been able to expand large numbers of viable and functional human gammadelta-T cells, an undertaking until now notpossible. As important, these apoptosis-resistant gammadelta-T cells appear to retain major histocompatibility complex-unrestricted (innate) antitumor activity against a wide variety of human tumor cells both in vitro and in vivo. Moreover, apoptosis-resistant gammadelta-T cells also display potent innate antiviral activity in vitro against human immunodeficiency virus-1. Both the biologic and practical implications of these findings are considered and discussed particularly as they relate to the development of future adoptive immunotherapy strategies.
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