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REVIEW article

Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
Volume 12 - 2024 | doi: 10.3389/fcell.2024.1511931

Novel gene manipulation approaches to unlock the existing bottlenecks of CAR-NK cell therapy

Provisionally accepted
Fatemeh Dehghan Fatemeh Dehghan 1Yekta Metanat Yekta Metanat 2Mandana Askarizadeh Mandana Askarizadeh 3Ehsan Ahmadi Ehsan Ahmadi 4*Vahid Moradi Vahid Moradi 5*
  • 1 Department of Anatomy and Molecular Biology, Shahid Sadoughi University of Medical Sciences,, Yazd, Iran
  • 2 Faculty of Medicine, Zahedan University of Medical Sciences, Sistan and Baluchestan Province, Iran
  • 3 School of Biology and Ecology, University of Maine, Orono, United States
  • 4 Department of Medical Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  • 5 Department of Hematology and Blood Transfusion Sciences, School of Allied Medicine, Tehran University of Medical Sciences, Tehran, Iran

The final, formatted version of the article will be published soon.

    Currently, CAR-T cell therapy is known as an efficacious treatment for patients with relapsed/refractory hematologic malignancies. Nonetheless, this method faces several bottlenecks, including low efficacy for solid tumors, lethal adverse effects, high cost of autologous products, and the risk of GvHD in allogeneic settings. As a potential alternative, CAR-NK cell therapy can overcome most of the limitations of CAR-T cell therapy and provide an off-the-shelf, safer, and more affordable product. Although published results from preclinical and clinical studies with CAR-NK cells are promising, several bottlenecks must be unlocked to maximize the effectiveness of CAR-NK cell therapy. These bottlenecks include low in vivo persistence, low trafficking into tumor sites, modest efficacy in solid tumors, and sensitivity to immunosuppressive tumor microenvironment. In recent years, advances in gene manipulation tools and strategies have laid the groundwork to overcome the current bottlenecks of CAR-NK cell therapy. This review will introduce the existing gene manipulation tools and discuss their advantages and disadvantages. We will also explore how these tools can enhance CAR-NK cell therapy's safety and efficacy.

    Keywords: CAR-NK, chimeric antigen receptor (CAR), Genetic Engineering, gene editing, Immunotherapy, CRISPR/Cas9, Neoplasms

    Received: 15 Oct 2024; Accepted: 10 Dec 2024.

    Copyright: © 2024 Dehghan, Metanat, Askarizadeh, Ahmadi and Moradi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Ehsan Ahmadi, Department of Medical Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
    Vahid Moradi, Department of Hematology and Blood Transfusion Sciences, School of Allied Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.