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Genome Editing in Engineered T Cells for Cancer Immunotherapy

Bonini, Chiara; Chapuis, Aude G; Hudecek, Michael; Guedan, Sonia; Magnani, Chiara; Qasim, Waseem (2023). Genome Editing in Engineered T Cells for Cancer Immunotherapy. Human Gene Therapy, 34(17-18):853-869.

Abstract

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.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology and Hematology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Molecular Medicine
Life Sciences > Molecular Biology
Life Sciences > Genetics
Language:English
Date:10 September 2023
Deposited On:28 Nov 2023 14:21
Last Modified:26 Feb 2025 02:43
Publisher:Mary Ann Liebert
ISSN:1043-0342
OA Status:Closed
Publisher DOI:https://doi.org/10.1089/hum.2023.128
PubMed ID:37694593

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