High CD62L expression predicts the generation of chimeric antigen receptor T cells with potent effector functions.

Autor:	Kasuya H; Division of Immune Response, Aichi Cancer Center Research Institute, Nagoya, Japan., Zhang H; Division of Immune Response, Aichi Cancer Center Research Institute, Nagoya, Japan.; Department of Cancer Diagnostics and Therapeutics, Nagoya University Graduate School of Medicine, Nagoya, Japan.; Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan., Ito Y; Division of Immune Response, Aichi Cancer Center Research Institute, Nagoya, Japan.; Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan., Yoshikawa T; Division of Immune Response, Aichi Cancer Center Research Institute, Nagoya, Japan.; Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan., Nakashima T; Division of Immune Response, Aichi Cancer Center Research Institute, Nagoya, Japan.; Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.; Department of Hematology and Oncology, Nagoya City University Institute of Medical and Pharmaceutical Sciences, Nagoya, Japan., Li Y; Division of Immune Response, Aichi Cancer Center Research Institute, Nagoya, Japan.; Department of Cancer Diagnostics and Therapeutics, Nagoya University Graduate School of Medicine, Nagoya, Japan.; Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan., Matsukawa T; Division of Immune Response, Aichi Cancer Center Research Institute, Nagoya, Japan.; Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.; Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan., Inoue S; Division of Immune Response, Aichi Cancer Center Research Institute, Nagoya, Japan.; Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan., Kagoya Y; Division of Immune Response, Aichi Cancer Center Research Institute, Nagoya, Japan.; Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
Jazyk:	angličtina
Zdroj:	International immunology [Int Immunol] 2024 Jun 08; Vol. 36 (7), pp. 353-364.
DOI:	10.1093/intimm/dxae015
Abstrakt:	The efficient generation of chimeric antigen receptor (CAR) T cells is highly influenced by the quality of apheresed T cells. Healthy donor-derived T cells usually proliferate better than patients-derived T cells and are precious resources to generate off-the-shelf CAR-T cells. However, relatively little is known about the determinants that affect the efficient generation of CAR-T cells from healthy donor-derived peripheral blood mononuclear cells (PBMCs) compared with those from the patients' own PBMCs. We here examined the efficiency of CAR-T cell generation from multiple healthy donor samples and analyzed its association with the phenotypic features of the starting peripheral blood T cells. We found that CD62L expression levels within CD8+ T cells were significantly correlated with CAR-T cell expansion. Moreover, high CD62L expression within naïve T cells was associated with the efficient expansion of T cells with a stem cell-like memory phenotype, an indicator of high-quality infusion products. Intriguingly, genetic disruption of CD62L significantly impaired CAR-T cell proliferation and cytokine production upon antigen stimulation. Conversely, ectopic expression of a shedding-resistant CD62L mutant augmented CAR-T cell effector functions compared to unmodified CAR-T cells, resulting in improved antitumor activity in vivo. Collectively, we identified the surface expression of CD62L as a concise indicator of potent T-cell proliferation. CD62L expression is also associated with the functional properties of CAR-T cells. These findings are potentially applicable to selecting optimal donors to massively generate CAR-T cell products. (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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