Chimeric Antigen Receptor T Cells: Extending Translation from Liquid to Solid Tumors

Human Gene Therapy
Michael A Morgan, Axel Schambach

Abstract

Successful translation of chimeric antigen receptor (CAR) T cells designed to target and eradicate CD19+ lymphomas has emboldened scientists and physicians worldwide to explore the possibility of applying CAR T-cell technology to other tumor entities, including solid tumors. Next-generation strategies such as fourth-generation CARs (CAR T cells redirected for universal cytokine killing, also known as TRUCKs) designed to deliver immunomodulatory cytokines to the tumor microenvironment, dual CAR designs to improve tumor control, inclusion of suicide genes as safety switches, and precision genome editing are currently being investigated. One major ongoing goal is to determine how best to generate CAR T cells that modulate the tumor microenvironment, overcome tumor survival mechanisms, and thus allow broader applicability as universal allogeneic T-cell therapeutics. Development of state-of-the-art and beyond viral vector systems to deliver designer CARs coupled with targeted genome editing is expected to generate more effective off-the-shelf CAR T cells with activity against a greater number of cancer types and importantly solid tumors.

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Citations

Mar 23, 2021·Frontiers in Immunology·Darel Martínez BedoyaDenis Migliorini

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Methods Mentioned

BETA
genetic modification
xenograft

Clinical Trials Mentioned

NCT01735604
NCT01886976
NCT02658929
NCT00902044
NCT02208362
NCT00968760
NCT01497184
NCT01673867
NCT02267343
NCT02808442

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