Genome Editing in Engineered T Cells for Cancer Immunotherapy

Advanced gene transfer technologies and profound immunological insights have enabled substantial increases in the efficacy of anticancer adoptive cellular therapy (ACT). In recent years, the U.S. Food and Drug Administration and European Medicines Agency have approved six engineered T cell therapeut...

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Bibliographic Details
Published in:Human gene therapy Vol. 34; no. 17-18; p. 853
Main Authors: Bonini, Chiara, Chapuis, Aude G, Hudecek, Michael, Guedan, Sonia, Magnani, Chiara, Qasim, Waseem
Format: Journal Article
Language:English
Published: United States 01.09.2023
Subjects:
Anniversaries and Special Events
B-Lymphocytes
Gene Editing
Humans
Immunotherapy
Neoplasms - genetics
Neoplasms - therapy
T-Lymphocytes
United States
United States
CRISPR
CAR
TCR
ISSN:1557-7422, 1557-7422
Online Access:Get more information
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Summary:Advanced gene transfer technologies and profound immunological insights have enabled substantial increases in the efficacy of anticancer adoptive cellular therapy (ACT). In recent years, the U.S. Food and Drug Administration and European Medicines Agency have approved six engineered T cell therapeutic products, all chimeric antigen receptor-engineered T cells directed against B cell malignancies. Despite encouraging clinical results, engineered T cell therapy is still constrained by challenges, which could be addressed by genome editing. As RNA-guided Clustered Regularly Interspaced Short Palindromic Repeats technology passes its 10-year anniversary, we review emerging applications of genome editing approaches designed to (1) overcome resistance to therapy, including cancer immune evasion mechanisms; (2) avoid unwanted immune reactions related to allogeneic T cell products; (3) increase fitness, expansion capacity, persistence, and potency of engineered T cells, while preserving their safety profile; and (4) improve the ability of therapeutic cells to resist immunosuppressive signals active in the tumor microenvironment. Overall, these innovative approaches should widen the safe and effective use of ACT to larger number of patients affected by cancer.
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ISSN:1557-7422
1557-7422
DOI:10.1089/hum.2023.128