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Review
, 41 (8), 717-723

Unleashing the Therapeutic Potential of CAR-T Cell Therapy Using Gene-Editing Technologies

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Review

Unleashing the Therapeutic Potential of CAR-T Cell Therapy Using Gene-Editing Technologies

In-Young Jung et al. Mol Cells.

Abstract

Chimeric antigen receptor (CAR) T-cell therapy, an emerging immunotherapy, has demonstrated promising clinical results in hematological malignancies including B-cell malignancies. However, accessibility to this transformative medicine is highly limited due to the complex process of manufacturing, limited options for target antigens, and insufficient anti-tumor responses against solid tumors. Advances in gene-editing technologies, such as the development of Zinc Finger Nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs), and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9), have provided novel engineering strategies to address these limitations. Development of next-generation CAR-T cells using gene-editing technologies would enhance the therapeutic potential of CAR-T cell treatment for both hematologic and solid tumors. Here we summarize the unmet medical needs of current CAR-T cell therapies and gene-editing strategies to resolve these challenges as well as safety concerns of gene-edited CAR-T therapies.

Keywords: CAR-T cell; CRISPR/Cas9; gene editing.

Figures

Fig. 1
Fig. 1. Gene-editing strategies for development of next generation CAR-T cell therapies
Gene-editing technologies can resolve three unmet medical needs of CAR-T cell therapy. First, gene-editing allows development of universal off-the-shelf CAR-T cells by alleviating GvH and HvG. Second, gene-editing broadens the range of otherwise untargetable CAR target antigens by preventing CAR-T cell fratricide of. Third, gene-editing enhances anti-tumor responses by circumventing T-cell hypofunction caused by continuous activation and immunosuppressive TME, which may expand the use of CAR-T cell therapy for solid tumors.

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