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Cancer immunotherapy harnessing γδ T cells and programmed death‐1
Author(s) -
Tanaka Yoshimasa
Publication year - 2020
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12917
Subject(s) - immune system , immunotherapy , adoptive cell transfer , cancer immunotherapy , antigen , cancer research , effector , immunology , cancer cell , cancer , biology , t cell , genetics
Cancer immunotherapy has received increasing attention since the success of CTLA‐4 and programmed death‐1 (PD‐1) immune checkpoint inhibitors and CAR‐T cells. One of the most promising next‐generation cancer treatments is adoptive transfer of immune effector cells. Developing an efficacious adoptive transfer therapy requires growing large numbers of highly purified immune effector cells in a short period of time. γδ T cells can be effectively expanded using synthetic antigens such as pyrophosphomonoesters and nitrogen‐containing bisphosphonates (N‐BPs). Pyrophosphomonoester antigens, initially identified in mycobacterial extracts, were used for this purpose in the early years of the development of γδ T cell‐based therapy. GMP‐grade N‐BPs, which are now commercially available, are used in many clinical trials worldwide. In order to develop N‐BPs for cancer immunotherapy, N‐BP prodrugs have been synthesized; among these, tetrakis‐pivaloyloxymethyl 2‐(thiazole‐2‐ylamino)ethylidene‐1,1‐bisphosphonate (PTA) is the most potent compound for stimulating γδ T cells. The activated γδ T cells express high levels of PD‐1, suggesting the potential for a combination therapy harnessing γδ T cells and PD‐1 immune checkpoint inhibitors. In addition, the functions of γδ T cells can be modified by IL‐18. Collectively, the recent findings show that γδ T cells are one of the most promising immune effector subsets for the development of novel cancer immunotherapy.