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Review
. 2025 Jul;27(7):795-811.
doi: 10.1016/j.jcyt.2025.05.010. Epub 2025 May 23.

The next innovations in chimeric antigen receptor T cell immunotherapies for cancer

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Free article
Review

The next innovations in chimeric antigen receptor T cell immunotherapies for cancer

Kusala Anupindi et al. Cytotherapy. 2025 Jul.
Free article

Abstract

Chimeric antigen receptor (CAR) T cell therapy has transformed cancer treatment and the field of immunotherapy. Although CAR T cell therapy has demonstrated considerable clinical success for the treatment of B cell malignancies, expanding its therapeutic efficacy and accessibility for other hematological malignancies and solid tumors remains a challenge. Key limitations include manufacturing constraints and therapeutic hurdles, such as CAR T cell persistence, proliferation, tumor trafficking and treatment-related toxicities. To overcome the unique challenges associated with CAR T cell therapy, novel technological advancements in CAR design, delivery, and T cell functionality can be leveraged. This review will explore three innovative approaches: gene editing and silencing, armoring strategies and in vivo CAR gene delivery. These approaches are all aimed at enhancing the accessibility and therapeutic efficacy of CAR T cell therapy in hematological malignancies.

Keywords: CAR T cell therapy; T cell; advanced therapies; cancer immunotherapy; cellular therapy; gene therapy.

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Conflict of interest statement

Declaration of Competing Interest C.H.J. is an inventor on patents and/or patent applications licensed to Novartis Institutes of Biomedical Research and Kite Pharma and receives license revenue from such licenses. C.H.J is a scientific founder of Dispatch Therapeutics, Bluewhale Bio and Capstan Therapeutics. C.H.J is a member of the scientific advisory boards of AC Immune, Alaunos. BLL is an inventor on patents or patent applications licensed to Novartis Institutes of Biomedical Research and Kite Pharma and receives license revenue from such licenses. BLL is a scientific founder of Tmunity Therapeutics and Capstan Therapeutics and is a member of the scientific advisory boards of Avectas, Capstan Therapeutics, Cellula Therapeutics, Immuneel Therapeutics, Immusoft, In8bio, Kite Gilead, Ori Biotech, Oxford Biomedica, ThermoFisher Pharma Services and UTC Therapeutics. The remaining authors have no conflicts of interest to declare.

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