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REVIEW article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1489827
This article is part of the Research Topic Cellular Immunotherapy: Transforming Cancer Treatment View all 3 articles

Advances in CAR T Cell Therapy: Antigen Selection, Modifications, and Current Trials for Solid Tumors

Provisionally accepted
Safwaan H Khan Safwaan H Khan 1,2Yeonjoo Choi Yeonjoo Choi 3Mysore Veena Mysore Veena 1,3John K Lee John K Lee 1,4,5Daniel Sanghoon Shin Daniel Sanghoon Shin 1,3,5,6*
  • 1 Division of Hematology and Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, United States
  • 2 Department of Microbiology, Immunology, and Molecular Genetics, College of Life Sciences, University of California, Los Angeles, Los Angeles, California, United States
  • 3 VA Greater Los Angeles Healthcare System, Veterans Health Administration, United States Department of Veterans Affairs, Los Angeles, California, United States
  • 4 Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, United States
  • 5 Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, United States
  • 6 Molecular Biology Institute, College of Life Sciences, University of California, Los Angeles, Los Angeles, California, United States

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

    Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of hematologic malignancies, achieving remarkable clinical success with FDA-approved therapies targeting CD19 and BCMA. However, the extension of these successes to solid tumors remains limited due to several intrinsic challenges, including antigen heterogeneity and immunosuppressive tumor microenvironments. In this review, we provide a comprehensive overview of recent advances in CAR T cell therapy aimed at overcoming these obstacles. We discuss the importance of antigen identification by emphasizing the identification of tumor-specific and tumor-associated antigens and the development of CAR T therapies targeting these antigens. Furthermore, we highlight key structural innovations, including cytokine-armored CARs, protease-regulated CARs, and CARs engineered with chemokine receptors, to enhance tumor infiltration and activity within the immunosuppressive microenvironment. Additionally, novel manufacturing approaches, such as the Sleeping Beauty transposon system, mRNA-based CAR transfection, and in vivo CAR T cell production, are discussed as scalable solution to improve the accessibility of CAR T cell therapies. Finally, we address critical therapeutic limitations, including cytokine release syndrome (CRS),

    Keywords: CAR T cell, solid tumors, Immunotherapy, Cancer, Structure, targets Current Trials, Challenges, and Promises (1

    Received: 01 Sep 2024; Accepted: 02 Dec 2024.

    Copyright: © 2024 Khan, Choi, Veena, Lee and Shin. 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: Daniel Sanghoon Shin, Division of Hematology and Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, 90095, California, United States

    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.