REVIEW article

Front. Immunol.

Sec. Cancer Immunity and Immunotherapy

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1512494

This article is part of the Research Topic Advancements and Challenges in CAR-T Cell Therapy for Cancer Treatment View all articles

Provisionally accepted

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

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Chimeric antigen receptor-engineered T cell therapies (CAR-T) are becoming powerful immunotherapeutic tools for treating malignancies, especially hematological malignancies. Like other biological drugs, CAR-T cell products can trigger unwanted immune responses in patients receiving the treatment. This might lead to treatment failure or life-threatening consequences. This immunogenicity could also affect the CAR-T cells' cellular kinetics and clinical responses. In this review, we summarize the immunogenicity of biologics and their effects on PK/PD profiles, safety, and efficacy. We also introduce the mechanisms of immunogenicity induced by CAR-T cells and clinical evidence of immunogenicity of the currently FDA-approved CAR-T cell products. Particularly, we summarize the currently available immunogenicity data from each CAR-T cell product's clinical trials, immunogenicity assays, sample types, and preclinical efficacy models, which were retrieved from the FDA and EMA websites. We also discuss a preclinical model that is promising for evaluating CAR-T cell immunogenicity.

Keywords: car-t, Immunogenicity, Anti-drug antibody (ADA), Biologics, Cellular Kinetics, clinical monitoring

Received: 16 Oct 2024; Accepted: 31 Jan 2025.

Copyright: © 2025 . 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.

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