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Updated: Jun 23, 2025
Production of Human CRISPR-Engineered CAR-T Cells
Published on: March 15, 2021
Progress and pitfalls of gene editing technology in CAR-T cell therapy: a state-of-the-art review
Vahid Moradi1, Elnaz Khodabandehloo2, Mehdi Alidadi3
1Hematology and Blood Transfusion Science Department, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran.
Abstract:
CAR-T cell therapy has shown remarkable promise in treating B-cell malignancies, which has sparked optimism about its potential to treat other types of cancer as well. Nevertheless, the Expectations of CAR-T cell therapy in solid tumors and non-B cell hematologic malignancies have not been met. Furthermore, safety concerns regarding the use of viral vectors and the current personalized production process are other bottlenecks that limit its widespread use. In recent years the use of gene editing technology in CAR-T cell therapy has opened a new way to unleash the latent potentials of CAR-T cell therapy and lessen its associated challenges. Moreover, gene editing tools have paved the way to manufacturing CAR-T cells in a fully non-viral approach as well as providing a universal, off-the-shelf product. Despite all the advantages of gene editing strategies, the off-target activity of classical gene editing tools (ZFNs, TALENs, and CRISPR/Cas9) remains a major concern. Accordingly, several efforts have been made in recent years to reduce their off-target activity and genotoxicity, leading to the introduction of advanced gene editing tools with an improved safety profile. In this review, we begin by examining advanced gene editing tools, providing an overview of how these technologies are currently being applied in clinical trials of CAR-T cell therapies. Following this, we explore various gene editing strategies aimed at enhancing the safety and efficacy of CAR-T cell therapy.
Insights
Gene editing enhances CAR-T cell therapy for solid tumors and non-B cell cancers. Advanced tools improve safety and efficacy, overcoming limitations of viral vectors and personalized production.
Area of Science:
- Immunotherapy
- Cancer Biology
- Gene Editing Technology
Background:
- Chimeric antigen receptor (CAR)-T cell therapy shows promise for B-cell malignancies.
- CAR-T therapy faces challenges in solid tumors and non-B-cell hematologic malignancies, including safety concerns and production bottlenecks.
- Gene editing offers potential solutions to enhance CAR-T cell therapy's scope and overcome existing limitations.
Purpose of the Study:
- To review advanced gene editing tools for CAR-T cell therapy.
- To examine the application of gene editing in current CAR-T clinical trials.
- To explore strategies for improving CAR-T safety and efficacy using gene editing.
Main Methods:
- Review of scientific literature on gene editing technologies (ZFNs, TALENs, CRISPR/Cas9, and newer variants).
- Analysis of clinical trial data incorporating gene-edited CAR-T cells.
- Exploration of gene editing strategies to mitigate off-target effects and genotoxicity.
Main Results:
- Gene editing enables non-viral CAR-T cell manufacturing and development of universal, off-the-shelf products.
- Advanced gene editing tools demonstrate reduced off-target activity and improved safety profiles compared to classical methods.
- Gene editing strategies are being actively investigated and applied in clinical trials for various cancers.
Conclusions:
- Gene editing significantly advances CAR-T cell therapy, expanding its potential beyond B-cell malignancies.
- Improved gene editing tools are crucial for enhancing the safety and efficacy of CAR-T therapies.
- Further research and clinical application of gene editing in CAR-T therapy hold promise for broader cancer treatment.
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