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SYSTEMATIC REVIEW article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1409665
This article is part of the Research Topic Achilles Heel of CAR T-Cell Therapy View all 3 articles

Modular (universal) CAR-T Platforms in vivo: A Comprehensive Systematic Review

Provisionally accepted
Afraa Mohammad Afraa Mohammad Anna A Yurina Anna A Yurina Tatiana Robertovna Simonyan Tatiana Robertovna Simonyan Daniil Sergeevich Chistyakov Daniil Sergeevich Chistyakov Rand Salman Rand Salman Ksenia Zornikova Ksenia Zornikova Elizaveta Petrovna Minina Elizaveta Petrovna Minina Apollinariya Vassilyevna Bogolyubova Apollinariya Vassilyevna Bogolyubova *
  • National Medical Research Center for Hematology, Moscow, Russia

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

    Background: Modular (universal) CAR T-platforms were developed to combat the limitations of traditional CAR-T therapy, allowing for multiple targeting of tumor-associated antigens and the ability to control CAR-T cell activity. The modular CAR-T platform consists of a universal receptor (signaling module) that recognizes an adapter molecule on the soluble module, which is responsible for antigen recognition. Multiple platforms have been developed over the last 12 years, and some of them have entered the clinical trial phase. This systematic review seeks to evaluate the different parameters of modular CAR-T platforms performance in animal models.A systematic search of literature in the PubMed database and in Google Scholar and BASE (Bielefeld Academic Search Engine) search engines was performed according to predefined eligibility criteria. All studies conducted on xenograft mouse models with any variant of modular CAR-T platforms were included. Forest plots were generated for visual presentation of the extracted quantitative findings (standardized mean difference (SMD) and median survival rate (MSR)).Results: A total of 33 studies employing 15 different modular CAR-T platforms were included. The platforms varied in terms of CAR-T cells, soluble module doses, and their frequency of administration. The studies showed a reduction in tumor burden and in tumor volume compared to the combined negative group. In comparison with the positive control group, there was no significant change in tumor burden or volume. In all the included studies the experimental group had a higher survival probability compared to the combined negative group at the study endpoint, with no significant difference in survival rate compared to the positive control group.The modular CAR-T platforms are generally effective and are a valuable addition to the arsenal of CAR therapy.

    Keywords: Modular CAR T, Universal CAR T, Xenograft model, Pre-clinical study, Systematic review

    Received: 30 Mar 2024; Accepted: 14 Nov 2024.

    Copyright: © 2024 Mohammad, Yurina, Simonyan, Chistyakov, Salman, Zornikova, Minina and Bogolyubova. 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: Apollinariya Vassilyevna Bogolyubova, National Medical Research Center for Hematology, Moscow, Russia

    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.