Translating gammadelta (γδ) T cells and their receptors into cancer cell therapies
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Translating gammadelta (γδ) T cells and their receptors into cancer cell therapies. / Sebestyen, Zsolt; Prinz, Immo; Déchanet-Merville, Julie; Silva-Santos, Bruno; Kuball, Jurgen.
In: NAT REV DRUG DISCOV, Vol. 19, No. 3, 03.2020, p. 169-184.Research output: SCORING: Contribution to journal › SCORING: Review article › Research
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TY - JOUR
T1 - Translating gammadelta (γδ) T cells and their receptors into cancer cell therapies
AU - Sebestyen, Zsolt
AU - Prinz, Immo
AU - Déchanet-Merville, Julie
AU - Silva-Santos, Bruno
AU - Kuball, Jurgen
PY - 2020/3
Y1 - 2020/3
N2 - Clinical responses to checkpoint inhibitors used for cancer immunotherapy seemingly require the presence of αβT cells that recognize tumour neoantigens, and are therefore primarily restricted to tumours with high mutational load. Approaches that could address this limitation by engineering αβT cells, such as chimeric antigen receptor T (CAR T) cells, are being investigated intensively, but these approaches have other issues, such as a scarcity of appropriate targets for CAR T cells in solid tumours. Consequently, there is renewed interest among translational researchers and commercial partners in the therapeutic use of γδT cells and their receptors. Overall, γδT cells display potent cytotoxicity, which usually does not depend on tumour-associated (neo)antigens, towards a large array of haematological and solid tumours, while preserving normal tissues. However, the precise mechanisms of tumour-specific γδT cells, as well as the mechanisms for self-recognition, remain poorly understood. In this Review, we discuss the challenges and opportunities for the clinical implementation of cancer immunotherapies based on γδT cells and their receptors.
AB - Clinical responses to checkpoint inhibitors used for cancer immunotherapy seemingly require the presence of αβT cells that recognize tumour neoantigens, and are therefore primarily restricted to tumours with high mutational load. Approaches that could address this limitation by engineering αβT cells, such as chimeric antigen receptor T (CAR T) cells, are being investigated intensively, but these approaches have other issues, such as a scarcity of appropriate targets for CAR T cells in solid tumours. Consequently, there is renewed interest among translational researchers and commercial partners in the therapeutic use of γδT cells and their receptors. Overall, γδT cells display potent cytotoxicity, which usually does not depend on tumour-associated (neo)antigens, towards a large array of haematological and solid tumours, while preserving normal tissues. However, the precise mechanisms of tumour-specific γδT cells, as well as the mechanisms for self-recognition, remain poorly understood. In this Review, we discuss the challenges and opportunities for the clinical implementation of cancer immunotherapies based on γδT cells and their receptors.
KW - Cell- and Tissue-Based Therapy/methods
KW - Humans
KW - Immunotherapy/methods
KW - Neoplasms/immunology
KW - Receptors, Antigen, T-Cell, gamma-delta/immunology
KW - T-Lymphocytes/immunology
U2 - 10.1038/s41573-019-0038-z
DO - 10.1038/s41573-019-0038-z
M3 - SCORING: Review article
C2 - 31492944
VL - 19
SP - 169
EP - 184
JO - NAT REV DRUG DISCOV
JF - NAT REV DRUG DISCOV
SN - 1474-1776
IS - 3
ER -