1. Engineering Next-Generation CAR-T Cells for Better Toxicity Management
- Author
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Andrea, Alain E., Chiron, Andrada, Bessoles, Stephanie, Hacein-Bey-Abina, Salima, Université Saint-Joseph de Beyrouth (USJ), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Institut de Chimie du CNRS (INC)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), ORANGE, Colette, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
- Subjects
EXPRESSION ,[SDV.BIO]Life Sciences [q-bio]/Biotechnology ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,SUICIDE GENE-THERAPY ,ANTITUMOR-ACTIVITY ,SAFETY SWITCH ,DONOR LYMPHOCYTES ,EFFICACY ,CANCER ,CHIMERIC ANTIGEN RECEPTOR ,[SDV.BIO] Life Sciences [q-bio]/Biotechnology ,ACTIVATION ,ANTIBODY ,[SDV.IMM]Life Sciences [q-bio]/Immunology - Abstract
International audience; Immunoadoptive therapy with genetically modified T lymphocytes expressing chimeric antigen receptors (CARs) has revolutionized the treatment of patients with hematologic cancers. Although clinical outcomes in B-cell malignancies are impressive, researchers are seeking to enhance the activity, persistence, and also safety of CAR-T cell therapy-notably with a view to mitigating potentially serious or even life-threatening adverse events like on-target/off-tumor toxicity and (in particular) cytokine release syndrome. A variety of safety strategies have been developed by replacing or adding various components (such as OFF- and ON-switch CARs) or by combining multi-antigen-targeting OR-, AND- and NOT-gate CAR-T cells. This research has laid the foundations for a whole new generation of therapeutic CAR-T cells. Here, we review the most promising CAR-T cell safety strategies and the corresponding preclinical and clinical studies.
- Published
- 2020