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Engineering Next-Generation CAR-T Cells for Better Toxicity Management.

ABSTRACT: 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.

SUBMITTER: Andrea AE

PROVIDER: S-EPMC7696189 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Engineering Next-Generation CAR-T Cells for Better Toxicity Management.

Andrea Alain E AE Chiron Andrada A Bessoles Stéphanie S Hacein-Bey-Abina Salima S

International journal of molecular sciences 20201116 22

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) cytokin ...[more]

PMID: 33207607

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