Triple-costimulatory GD2-CAR T cells incorporating CD28, 4-1BB and CD27 mediate potent cytotoxicity and reduce exhaustion in solid tumour models.

Jatuporn Sujjitjoon¹, Katesara Kongkla², Pornpimon Yuti², Nunghathai Sawasdee², Krissada Natungnuy², Naravat Poungvarin³, Pa-Thai Yenchitsomanus⁴

¹Siriraj Center of Research for Cancer Immunotherapy (SiCORE-CIT), and Division of Molecular Medicine, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. Electronic address: jatuporn.suj@mahidol.ac.th.

²Siriraj Center of Research for Cancer Immunotherapy (SiCORE-CIT), and Division of Molecular Medicine, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.

³Department of Clinical Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.

⁴Siriraj Center of Research for Cancer Immunotherapy (SiCORE-CIT), and Division of Molecular Medicine, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. Electronic address: pathai.yen@mahidol.ac.th.

PubMed DOI

Abstract

Disialoganglioside (GD2) is a validated tumour-associated antigen for chimeric antigen receptor (CAR) T-cell therapy; yet most GD2-CAR constructs carry limited costimulatory signaling, which may constrain efficacy and durability. We engineered humanised hu3F8-based GD2-CAR T cells bearing dual or triple costimulatory domains- GD2-28BBζ (CD28/4-1BB), GD2-28.27ζ (CD28/CD27) and GD2-28BB27ζ (CD28/4-1…

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