Modular (universal) CAR-T platforms in vivo: a comprehensive systematic review

BackgroundModular (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 mod...

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Main Authors: Afraa Mohammad, Anna Yurina, Tatiana Simonyan, Daniil Chistyakov, Rand Salman, Ksenia Zornikova, Elizaveta Minina, Apollinariya Bogolyubova
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1409665/full
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author Afraa Mohammad
Anna Yurina
Tatiana Simonyan
Daniil Chistyakov
Rand Salman
Ksenia Zornikova
Elizaveta Minina
Apollinariya Bogolyubova
author_facet Afraa Mohammad
Anna Yurina
Tatiana Simonyan
Daniil Chistyakov
Rand Salman
Ksenia Zornikova
Elizaveta Minina
Apollinariya Bogolyubova
author_sort Afraa Mohammad
collection DOAJ
description BackgroundModular (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.MethodsA 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)).ResultsA 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.ConclusionThe modular CAR-T platforms are generally effective and are a valuable addition to the arsenal of CAR therapy.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/ PROSPERO, identifier CRD42023443984.
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spelling doaj-art-251b93d4cc564e9a8c705caea4bb52662025-08-20T02:19:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.14096651409665Modular (universal) CAR-T platforms in vivo: a comprehensive systematic reviewAfraa MohammadAnna YurinaTatiana SimonyanDaniil ChistyakovRand SalmanKsenia ZornikovaElizaveta MininaApollinariya BogolyubovaBackgroundModular (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.MethodsA 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)).ResultsA 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.ConclusionThe modular CAR-T platforms are generally effective and are a valuable addition to the arsenal of CAR therapy.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/ PROSPERO, identifier CRD42023443984.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1409665/fullmodular CAR Tuniversal CAR Txenograft modelpre-clinical studysystematic review
spellingShingle Afraa Mohammad
Anna Yurina
Tatiana Simonyan
Daniil Chistyakov
Rand Salman
Ksenia Zornikova
Elizaveta Minina
Apollinariya Bogolyubova
Modular (universal) CAR-T platforms in vivo: a comprehensive systematic review
Frontiers in Immunology
modular CAR T
universal CAR T
xenograft model
pre-clinical study
systematic review
title Modular (universal) CAR-T platforms in vivo: a comprehensive systematic review
title_full Modular (universal) CAR-T platforms in vivo: a comprehensive systematic review
title_fullStr Modular (universal) CAR-T platforms in vivo: a comprehensive systematic review
title_full_unstemmed Modular (universal) CAR-T platforms in vivo: a comprehensive systematic review
title_short Modular (universal) CAR-T platforms in vivo: a comprehensive systematic review
title_sort modular universal car t platforms in vivo a comprehensive systematic review
topic modular CAR T
universal CAR T
xenograft model
pre-clinical study
systematic review
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1409665/full
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