首页|CRISPR,CAR-T,and NK:Current applications and future perspectives

CRISPR,CAR-T,and NK:Current applications and future perspectives

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Chimeric antigen receptor T(CAR-T)cell therapy represents a breakthrough in personalized cancer treatments.In this regard,synthetic receptors comprised of antigen recognition domains,signaling,and stimulatory domains are used to reprogram T-cells to target tum or cells and destroy them.Despite the success of this approach in refractory B-cell malignancies,the optimal potency of CAR T-cell therapy for many other cancers,particularly solid tumors,has not been validated.Natural killer cells are powerful cytotoxic lymphocytes specialized in recognizing and dispensing the tumor cells in coordination with other anti-tumor immunity cells.Based on these studies,many investigations are focused on the accurate designing of CAR T-cells with clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)system or other novel gene editing tools that can induce hereditary changes with or without the presence of a double-stranded break into the genome.These methodologies can be specifically focused on negative controllers of T-cells,induce modifications to a particular gene,and produce reproducible,safe,and powerful allogeneic CAR T-cells for on-demand cancer immunotherapy.The improvement of the CRISPR/Cas9 innovation offers an adaptable and proficient gene-editing capability in activating different pathways to help natural killer cells interact with novel CARs to particularly target tumor cells.Novel achievements and future challenges of combining next-generation CRISPR-Cas9 gene editing tools to optimize CAR T-cell and natural killer cell treatment for future clinical trials toward the foundation of modern cancer treatments have been assessed in this review.

CancerCAR T-cellCRISPRGene editingImmunotherapyNK cell

Mohadeseh Khoshandam、Hossein Soltaninejad、Amir Ali Hamidieh、Saman Hosseinkhani

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Department of Reproductive Biology,Academic Center for Education,Culture,and Research(ACECR),Qom branch 3716986466,Iran

National Institute of Genetic Engineering and Biotechnology(NIGEB),Tehran 14965/161,Iran

Department of stem cells technology and Tissue Regeneration,Faculty of Interdisciplinary Science and Technologies,Tarbiat Modares University,Tehran 15614,Iran

Pediatric Cell Therapy and Gene Therapy Research Center,Gene,Cell & Tissue Research Institute,Tehran University of Medical Sciences,Tehran 1417935840,Iran

Department of Biochemistry,Faculty of Biological Sciences,Tarbiat Modares University,Tehran 15614,Iran

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2024

10.1016/j.gendis.2023.101121

基因与疾病(英文)

基因与疾病(英文)

ISSN：
年,卷(期)：2024.11(4)