Skip to main content

REVIEW article

Front. Immunol.
Sec. Alloimmunity and Transplantation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1527648
This article is part of the Research Topic Balancing Alloantigen-Induced Immune Responses and Anti-tumor Immunity in Transplantation View all 6 articles

Alloreactive-free CAR-VST therapy: a step forward in long-term tumor control in viral context

Provisionally accepted
Valentine Wang Valentine Wang 1,2Barbara Savoldo Barbara Savoldo 3José-Arthur Guimaraes José-Arthur Guimaraes 2Gianpietro Dotti Gianpietro Dotti 3Loïc REPPEL Loïc REPPEL 2,4Daniele Bensoussan Daniele Bensoussan 2,4*
  • 1 Université de Lorraine, Nancy, France
  • 2 UMR7365 Ingénierie Moléculaire et Physiopathologie Articulaire (IMOPA), Vandœuvre-lès-Nancy, Lorraine, France
  • 3 Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • 4 Centre Hospitalier Universitaire de Nancy, Nancy, Lorraine, France

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

    CAR-T cell therapy has revolutionized immunotherapy but its allogeneic application, using various strategies, faces significant challenges including graft-versus-host disease and graft rejection. Recent advances using Virus Specific T cells to generate CAR-VST have demonstrated potential for enhanced persistence and antitumor efficacy, positioning CAR-VSTs as a promising alternative to conventional CAR-T cells in an allogeneic setting. This review provides a comprehensive overview of CAR-VST development, emphasizing strategies to mitigate immunogenicity, such as using a specialized TCR, and approaches to improve therapeutic persistence against host immune responses. In this review, we discuss the production methods of CAR-VSTs and explore optimization strategies to enhance their functionality, activation profiles, memory persistence, and exhaustion resistance. Emphasis is placed on their unique dual specificity for both antitumor and antiviral responses, along with an in-depth examination of preclinical and clinical outcomes. We highlight how these advances contribute to the efficacy and durability of CAR-VSTs in therapeutic settings, offering new perspectives for broad clinical applications. By focusing on the key mechanisms that enable CAR-VSTs to address autologous CAR-T cell challenges, this review highlights their potential as a promising strategy for developing effective allogeneic CAR-T therapies.

    Keywords: CAR-T1, Virus Specific T cell2, CAR-VST3, Allogeneic4, GvHD5, Graft rejection6

    Received: 13 Nov 2024; Accepted: 30 Dec 2024.

    Copyright: © 2024 Wang, Savoldo, Guimaraes, Dotti, REPPEL and Bensoussan. 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: Daniele Bensoussan, UMR7365 Ingénierie Moléculaire et Physiopathologie Articulaire (IMOPA), Vandœuvre-lès-Nancy, 54505, Lorraine, France

    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.