Center for Medical Ethics and Health Policy Staff Publications

Language

English

Publication Date

7-16-2024

Journal

Cell Reports Medicine

DOI

10.1016/j.xcrm.2024.101628

PMID

38986621

PMCID

PMC11293353

PubMedCentral® Posted Date

7-16-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Chimeric antigen receptor T cells (CART) targeting lymphocyte antigens can induce T cell fratricide and require additional engineering to mitigate self-damage. We demonstrate that the expression of a chimeric antigen receptor (CAR) targeting CD5, a prominent pan-T cell antigen, induces rapid internalization and complete loss of the CD5 protein on T cells, protecting them from self-targeting. Notably, exposure of healthy and malignant T cells to CD5.CART cells induces similar internalization of CD5 on target cells, transiently shielding them from cytotoxicity. However, this protection is short-lived, as sustained activity of CD5.CART cells in patients with T cell malignancies results in full ablation of CD5

Keywords

CD5 Antigens, Humans, Receptors, Chimeric Antigen, Cytotoxicity, Immunologic, T-Lymphocytes, Immunotherapy, Adoptive, Animals, Receptors, Antigen, T-Cell

Published Open-Access

yes

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