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D'Souza et al. J Cancer Metastasis Treat 2022;8:28 Journal of Cancer
DOI: 10.20517/2394-4722.2022.51
Metastasis and Treatment

Review Open Access

Overcoming tumor antigen heterogeneity in
CAR-T cell therapy for malignant mesothelioma (MM)

1
2
1
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Reena R. D'Souza 1 , Paraskevi Dimou , Reyisa Bughda , Elizabeth Hawkins , Clara Leboreiro Babe ,
Astero Klampatsa 1
1
Division of Cancer Therapeutics, The Institute of Cancer Research, London SM2 5NG, UK.
2
Division of Radiotherapy and Imaging, The Institute of Cancer Research, London SM2 5NG, UK.
Correspondence to: Dr. Astero Klampatsa, Division of Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road,
Sutton, London SM2 5NG, UK. E-mail: astero.klampatsa@icr.ac.uk
How to cite this article: D'Souza RR, Dimou P, Bughda R, Hawkins E, Leboreiro Babe C, Klampatsa A. Overcoming tumor antigen
heterogeneity in CAR-T cell therapy for malignant mesothelioma (MM). J Cancer Metastasis Treat 2022;8:28.
https://dx.doi.org/10.20517/2394-4722.2022.51

Received: 15 May 2022 First Decision: 9 Jun 2022 Revised: 15 Jun 2022 Accepted: 18 Jul 2022 Published: 28 Jul 2022
Academic Editor: Kamran Shaukat Copy Editor: Fangling Lan Production Editor: Fangling Lan

Abstract
Malignant mesothelioma (MM) is a rare, aggressive solid tumor with limited therapeutic options and poor
therapeutic response. The role of immunotherapy in MM is now well established and therapeutic options, such as
checkpoint inhibitors, are increasingly being approved. Chimeric antigen receptor (CAR)-T cell therapy is
successfully implemented in several hematologic cancers, but currently has inadequate effect in solid tumors,
owing to several limitations, such as trafficking and infiltration, limited T cell persistence and exhaustion, the
immunosuppressive TME and tumor antigen heterogeneity. The lack of uniform and universal expression of tumor-
associated antigens (TAAs) on tumor cells, as well as TAA heterogeneity following tumor editing post-therapy, are
issues of significant importance to CAR-T cell and associated antigen-targeting therapies. Our review discusses the
concept of tumor antigen heterogeneity in MM, the consequences for CAR-T cell therapies and the strategies to
overcome it.

Keywords: Antigen heterogeneity, chimeric antigen receptor (CAR) T cells, mesothelioma, tumor-associated
antigens (TAAs), bystander effect, epitope spreading, tumor microenvironment

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
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