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Review | Open Access

Boosting CAR-T cell therapy with CRISPR technology

Liyanran Yan1,#Shanzi Gao2,#Xinhui Wang3,#Xintao Zhou4Praopim Limsakul5Yiqian Wu6( )
Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
College of Biological Sciences & Biotechnology, Beijing Forestry University, Beijing, China
SDU-ANU Joint Science College, Shandong University, Shandong, China
College of Chemistry, South China Normal University, Guangdong, China
Division of Physical Science, Faculty of Science, and Center of Excellence for Trace Analysis and Biosensor, Prince of Songkla University, Songkhla, Thailand
National Biomedical Imaging Center, Peking University, Beijing, China

#These authors contributed equally to this work

Show Author Information

Highlights

● Various issues of chimeric antigen receptor (CAR)-T cell therapy exist that hinder its broad application in cancer treatment.

● Clustered regularly interspaced short palindromic repeats (CRISPR) technologies provide powerful tools for genetic and epigenetic reprogramming.

● CRISPR and its derived technologies have been applied to address the issues in CAR-T cell therapy regarding its safety and effectiveness via specific targeting of known genes and CRISPR-based screening.

● Risks exist in CRISPR/CRISPR-associated protein 9 (Cas9)-based editing, which calls for careful evaluation and further studies on the mechanisms and solutions.

Graphical Abstract

Abstract

Chimeric antigen receptor (CAR)-T cell therapy has made remarkable breakthroughs in treating cancers, especially hematologic malignancies, yet its broader application in cancer treatment is hindered by multiple challenges. Meanwhile, the development of clustered regularly interspaced short palindromic repeats (CRISPR) and its derived technologies has provided unprecedentedly efficient tools for genomic and cellular reprogramming, offering potential advantages for developing CAR-T cell therapy. There is hence a rapidly increasing interest in applying CRISPR to engineer CART cells. Here, we present a review of recent research utilizing CRISPR to boost CAR-T cell therapy by enhancing its safety or effectiveness. We first provide an overview of CAR-T cell therapy and CRISPR technology, followed by discussions on how CRISPR and its related technologies can be adopted to tackle various issues associated with CAR-T cell therapy, either via knockout/knockin of specific genes or CRISPR-based screening. We also summarize clinical trials involving CRISPR-edited CAR-T cells. Lastly, we address the potential risks of applying CRISPR in CAR-T cell engineering.

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hLife
Pages 380-396
Cite this article:
Yan L, Gao S, Wang X, et al. Boosting CAR-T cell therapy with CRISPR technology. hLife, 2024, 2(8): 380-396. https://doi.org/10.1016/j.hlife.2024.06.002

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Received: 12 March 2024
Revised: 03 June 2024
Accepted: 05 June 2024
Published: 08 June 2024
© 2024 The Authors.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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