Repository of Research and Investigative Information

Repository of Research and Investigative Information

Ilam University of Medical Sciences

Site-specific transgene integration in chimeric antigen receptor (CAR) T cell therapies

Mon Feb 26 05:38:33 2024

(2023) Site-specific transgene integration in chimeric antigen receptor (CAR) T cell therapies. Biomarker Research. p. 23.

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Abstract

Chimeric antigen receptor (CAR) T cells and natural killer (NK) cells are genetically engineered immune cells that can detect target antigens on the surface of target cells and eliminate them following adoptive transfer. Recent progress in CAR-based therapies has led to outstanding clinical success in certain patients with leukemias and lymphomas and offered therapeutic benefits to those resistant to conventional therapies. The universal approach to stable CAR transgene delivery into the T/NK cells is the use of viral particles. Such approaches mediate semi-random transgene insertions spanning the entire genome with a high preference for integration into sites surrounding highly-expressed genes and active loci. Regardless of the variable CAR expression level based on the integration site of the CAR transgene, foreign integrated DNA fragments may affect the neighboring endogenous genes and chromatin structure and potentially change a transduced T/NK cell behavior and function or even favor cellular transformation. In contrast, site-specific integration of CAR constructs using recent genome-editing technologies could overcome the limitations and disadvantages of universal random gene integration. Herein, we explain random and site-specific integration of CAR transgenes in CAR-T/NK cell therapies. Also, we tend to summarize the methods for site-specific integration as well as the clinical outcomes of certain gene disruptions or enhancements due to CAR transgene integration. Also, the advantages and limitations of using site-specific integration methods are discussed in this review. Ultimately, we will introduce the genomic safe harbor (GSH) standards and suggest some appropriate safety prospects for CAR integration in CAR-T/NK cell therapies.

Item Type: Article
Creators:
CreatorsEmail
Dabiri, H.UNSPECIFIED
Kozani, P. S.UNSPECIFIED
Anbouhi, M. H.UNSPECIFIED
Godarzee, M. M.UNSPECIFIED
Haddadi, M. H.UNSPECIFIED
Basiri, M.UNSPECIFIED
Ziaei, V.UNSPECIFIED
Sadeghizadeh, M.UNSPECIFIED
Saffar, E. H.UNSPECIFIED
Keywords: Chimeric antigen receptor Cancer immunotherapy Genome-editing technologies Retroviral vectors Natural killer cells gene-therapy noncoding rnas aavs1 locus crispr-cas genome immunotherapy target efficacy vector ccr5 Oncology Research & Experimental Medicine
Divisions:
Page Range: p. 23
Journal or Publication Title: Biomarker Research
Journal Index: ISI
Volume: 11
Number: 1
Identification Number: https://doi.org/10.1186/s40364-023-00509-1
Depositing User: مهندس مهدی شریفی
URI: http://eprints.medilam.ac.ir/id/eprint/4479

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