Chimeric Antigen Receptor (CAR) T-Cell Therapy for Thoracic Malignancies

Our plain-English summary of Chimeric Antigen Receptor (CAR) T-Cell Therapy for Thoracic Malignancies, by S. Kiesgen, L. Chicaybam, N.K. Chintala, et al (Journal of Thoracic Oncology, 2018).

The study

• Authors: S. Kiesgen, L. Chicaybam, N.K. Chintala, P.S. Adusumilli
• Journal: Journal of Thoracic Oncology
• Published: 2018;13(1):16-26
• Type of article: Review
• Cited by: 69 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Chimeric antigen receptor (CAR) T cells are patient T cells that are transduced with genetically engineered synthetic receptors to target a cancer cell surface antigen. The remarkable clinical response rates achieved by adoptive transfer of T cells that target CD19 in patients with leukemia and lymphoma have led to a growing number of clinical trials exploring CAR T-cell therapy for solid tumors. Herein, we review the evolution of adoptive T-cell therapy; highlight advances in CAR T-cell therapy for thoracic malignancies; and summarize the targets being investigated in clinical trials for patients with lung cancer, malignant pleural mesothelioma, and esophageal cancer. We further discuss the barriers to successfully translating CAR T-cell therapy for solid tumors and present strategies that have been investigated to overcome these hurdles.

Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

In plain English

This article was a review, not an original study, and reported no new treatment results; its figures included staining images of patient tumors illustrating obstacles to the therapy. The authors explained how chimeric antigen receptor (CAR) T-cell therapy works: a patient's own T cells are genetically engineered to recognize a target on cancer cells. They summarized the targets being tested in clinical trials for lung cancer, malignant pleural mesothelioma and esophageal cancer, drawing on trials listed on ClinicalTrials.gov as of 20 July 2017. For mesothelioma, they described mesothelin, a protein that earlier work by their own laboratory and others found overexpressed in 80 to 90% of malignant pleural mesothelioma. They also described fibroblast activating protein (FAP), which is expressed in all major mesothelioma subtypes, and noted their own Phase I safety trial of mesothelin-targeted CAR T cells given regionally to patients with pleural cancers. They wrote that using CAR T cells against solid tumors has proven challenging and named uneven target expression on tumor cells as one major hurdle. The article did not study asbestos exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of CAR T-cell therapy and the clinical trials of it for thoracic cancers
• Who was studied: No new treatment results were reported. The review compiled CAR T-cell clinical trials for thoracic cancers (lung cancer, malignant pleural mesothelioma, esophageal cancer) listed on ClinicalTrials.gov, last checked 20 July 2017. Its figures included staining images of patient tumors.
• Exposure: Not an exposure study; asbestos is not examined. The subject is CAR T-cell therapy, in which a patient's T cells are genetically engineered to target antigens on cancer cells, such as mesothelin, FAP, EGFR and HER2
• Main results:
  • A figure showed multiplex immunofluorescence staining of patient tumors. The authors used it to illustrate key obstacles to CAR T-cell therapy for thoracic malignancies.
  • The review cited earlier work by the authors' laboratory and others finding mesothelin overexpressed on cancer cells in 80 to 90% of malignant pleural mesothelioma (MPM)
  • The review described FAP as a potential target expressed in all of the major MPM histologic subtypes
  • The authors reported that their group is running a Phase I trial (NCT02414269) to evaluate the safety of regionally given mesothelin-targeted CAR T cells in patients with primary or secondary pleural malignancies
  • The authors wrote that using CAR T cells to treat solid tumors has proven challenging. They described variability of antigen expression on tumor cells as one of the major hurdles.
• The authors' conclusion: The authors concluded that bringing together advances in T-cell biology, tumor biology and the tumor microenvironment will provide tools to enhance CAR T-cell function and efficacy, and ultimately improve clinical responses in patients with thoracic malignancies

Topics

Medical terms in this study, explained in our Lexicon: Clinical Trial, Lung Cancer, Pleural Mesothelioma, Esophageal Cancer.

Related studies

• Mesothelin as a target for chimeric antigen receptor-modified T cells as anticancer therapy — M. O'Hara, C. Stashwick, et al. (2016)
• T cells expressing chimeric antigen receptors can cause anaphylaxis in humans — M.V. Maus, A.R. Haas, et al. (2013)
• Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies — G.L. Beatty, A.R. Haas, et al. (2014)
• Proton therapy for thoracic malignancies: a review of oncologic outcomes — N.V. Patel, N.Y. Yu, et al. (2021)
• Clinical Evaluation of ErbB-Targeted CAR T-Cells, Following Intracavity Delivery in Patients with ErbB-Expressing Solid Tumors — S. Papa, M. van Schalkwyk, et al. (2015)
• Generation of Potent T-cell Immunotherapy for Cancer Using DAP12-Based, Multichain, Chimeric Immunoreceptors — E. Wang, L.C. Wang, et al. (2015)

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