TY - JOUR
T1 - ‘Off-the-shelf’ allogeneic CAR T cells
T2 - development and challenges
AU - Depil, S.
AU - Duchateau, P.
AU - Grupp, S. A.
AU - Mufti, G.
AU - Poirot, L.
N1 - Publisher Copyright:
© 2020, Springer Nature Limited.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - Autologous chimeric antigen receptor (CAR) T cells have changed the therapeutic landscape in haematological malignancies. Nevertheless, the use of allogeneic CAR T cells from donors has many potential advantages over autologous approaches, such as the immediate availability of cryopreserved batches for patient treatment, possible standardization of the CAR-T cell product, time for multiple cell modifications, redosing or combination of CAR T cells directed against different targets, and decreased cost using an industrialized process. However, allogeneic CAR T cells may cause life-threatening graft-versus-host disease and may be rapidly eliminated by the host immune system. The development of next-generation allogeneic CAR T cells to address these issues is an active area of research. In this Review, we analyse the different sources of T cells for optimal allogeneic CAR-T cell therapy and describe the different technological approaches, mainly based on gene editing, to produce allogeneic CAR T cells with limited potential for graft-versus-host disease. These improved allogeneic CAR-T cell products will pave the way for further breakthroughs in the treatment of cancer.
AB - Autologous chimeric antigen receptor (CAR) T cells have changed the therapeutic landscape in haematological malignancies. Nevertheless, the use of allogeneic CAR T cells from donors has many potential advantages over autologous approaches, such as the immediate availability of cryopreserved batches for patient treatment, possible standardization of the CAR-T cell product, time for multiple cell modifications, redosing or combination of CAR T cells directed against different targets, and decreased cost using an industrialized process. However, allogeneic CAR T cells may cause life-threatening graft-versus-host disease and may be rapidly eliminated by the host immune system. The development of next-generation allogeneic CAR T cells to address these issues is an active area of research. In this Review, we analyse the different sources of T cells for optimal allogeneic CAR-T cell therapy and describe the different technological approaches, mainly based on gene editing, to produce allogeneic CAR T cells with limited potential for graft-versus-host disease. These improved allogeneic CAR-T cell products will pave the way for further breakthroughs in the treatment of cancer.
UR - http://www.scopus.com/inward/record.url?scp=85077451283&partnerID=8YFLogxK
U2 - 10.1038/s41573-019-0051-2
DO - 10.1038/s41573-019-0051-2
M3 - Review article
C2 - 31900462
AN - SCOPUS:85077451283
SN - 1474-1776
VL - 19
SP - 185
EP - 199
JO - Nature Reviews Drug Discovery
JF - Nature Reviews Drug Discovery
IS - 3
ER -
