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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.
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Contributor : Colette ORANGE Connect in order to contact the contributor
Submitted on : Friday, September 10, 2021 - 9:52:50 AM
Last modification on : Friday, August 5, 2022 - 11:57:41 AM


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Alain E. Andrea, Andrada Chiron, Stephanie Bessoles, Salima Hacein-Bey-Abina. Engineering Next-Generation CAR-T Cells for Better Toxicity Management. International Journal of Molecular Sciences, 2020, 21 (22), ⟨10.3390/ijms21228620⟩. ⟨hal-03295366⟩



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