Development of non-viral, ligand-dependent, EPHB4-specific chimeric antigen receptor T cells for treatment of rhabdomyosarcoma.

CAR-T cell therapy EPHB4 chimeric antigen receptor piggyBac transposon rhabdomyosarcoma stem cell memory-like T cells

Journal

Molecular therapy oncolytics
ISSN: 2372-7705
Titre abrégé: Mol Ther Oncolytics
Pays: United States
ID NLM: 101666776

Informations de publication

Date de publication:
26 Mar 2021
Historique:
received: 15 02 2021
accepted: 01 03 2021
entrez: 5 4 2021
pubmed: 6 4 2021
medline: 6 4 2021
Statut: epublish

Résumé

Ephrin type-B receptor 4 (EPHB4), expressed in tumors including rhabdomyosarcoma, is a suitable target for chimeric antigen receptor (CAR)-T cells. Ligand-independent activation of EPHB4 causes cell proliferation and malignant transformation in rhabdomyosarcoma, whereas ligand-dependent stimulation of EPHB4 induces apoptosis in rhabdomyosarcoma. Therefore, we hypothesized that ligand-based, EPHB4-specific CAR-T cells may kill rhabdomyosarcoma cells without stimulating downstream cell proliferation mechanisms. We developed novel CAR-T cells by targeting EPHB4 via EPHRIN B2, a natural ligand of EPHB4. The generation of EPHB4-CAR-T cells via

Identifiants

pubmed: 33816783
doi: 10.1016/j.omto.2021.03.001
pii: S2372-7705(21)00033-4
pmc: PMC7985479
doi:

Types de publication

Journal Article

Langues

eng

Pagination

646-658

Informations de copyright

© 2021 The Authors.

Déclaration de conflit d'intérêts

The authors declare no competing interests.

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Auteurs

Hiroshi Kubo (H)

Department of Pediatrics, Graduate School of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.

Shigeki Yagyu (S)

Department of Pediatrics, Graduate School of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.

Kayoko Nakamura (K)

Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.

Kumiko Yamashima (K)

Department of Pediatrics, Graduate School of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.

Akimasa Tomida (A)

Department of Pediatrics, Graduate School of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.

Ken Kikuchi (K)

Department of Pediatrics, Graduate School of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.

Tomoko Iehara (T)

Department of Pediatrics, Graduate School of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.

Yozo Nakazawa (Y)

Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.
Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Matsumoto, Japan.

Hajime Hosoi (H)

Department of Pediatrics, Graduate School of Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.

Classifications MeSH