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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

Clinical Evidence of Immunogenicity of CAR-T Cell Therapies and Its Implication in the Clinical Development of CAR-T Drug Products

Provisionally accepted
Hammodah R. Alfar Hammodah R. Alfar 1,2Cecil Chen Cecil Chen 3Eric Lachacz Eric Lachacz 4Weifeng Tang Weifeng Tang 2Yuqian Zhang Yuqian Zhang 2*
  • 1 Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentuck, Lexington, Kentucky, United States
  • 2 Clinical Pharmacology & Quantitative Pharmacology, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States
  • 3 Clinical Pharmacology & Quantitative Pharmacology, Biopharmaceuticals R&D, AstraZeneca, San Francisco, California, United States
  • 4 Integrated Bioanalysis, BioPharmaceuticals R&D, AstraZeneca, Mölndal, Sweden

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

    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 Alfar, Chen, Lachacz, Tang and Zhang. 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: Yuqian Zhang, Clinical Pharmacology & Quantitative Pharmacology, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, 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.