‘Off-the-shelf’ allogeneic CAR T cells: development and challenges

S. Depil*, P. Duchateau, S. A. Grupp, G. Mufti, L. Poirot

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

648 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)185-199
Number of pages15
JournalNature Reviews Drug Discovery
Volume19
Issue number3
DOIs
Publication statusPublished - 1 Mar 2020

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