Mesothelin-targeted agents in clinical trials and in preclinical development

Our plain-English summary of Mesothelin-targeted agents in clinical trials and in preclinical development, by R.J. Kelly, E. Sharon, I. Pastan, et al (Molecular Cancer Therapeutics, 2012).

The study

• Authors: R.J. Kelly, E. Sharon, I. Pastan, R. Hassan
• Journal: Molecular Cancer Therapeutics
• Published: 2012;11(3):517-25
• Type of article: Review
• Cited by: 89 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Mesothelin is a tumor differentiation antigen that is highly expressed in several malignant diseases in humans, including malignant mesothelioma and pancreatic, ovarian, and lung adenocarcinomas. The limited expression of mesothelin on normal human tissues and its high expression in many common cancers make it an attractive candidate for cancer therapy. Several agents, including an immunotoxin, monoclonal antibody, antibody drug conjugate, and tumor vaccine, are in various stages of development to treat patients with mesothelin-expressing tumors. This review highlights ongoing clinical trials, as well as other approaches to exploit mesothelin for cancer therapy, that are in preclinical development.

In plain English

This article was a review, not a new study. The authors, from the US National Cancer Institute, described treatments aimed at mesothelin. Mesothelin is a protein found on the normal cells lining the pleura, peritoneum and pericardium. It is found at high levels in malignant mesothelioma and in pancreatic, ovarian and lung adenocarcinomas. The authors reviewed early clinical trials of an immunotoxin (SS1P), an antibody (MORAb-009), a vaccine (CRS-207), engineered T cells and an antibody drug conjugate. They also covered approaches still being tested in the laboratory. In one of two trials of SS1P given alone, 34 patients were treated, and 4 of 33 evaluable patients had minor responses; the article's text reports 19 with disease stabilization, but its table gives 18. When SS1P was combined with pemetrexed and cisplatin for pleural mesothelioma, 7 of 14 evaluable patients had a partial response. MORAb-009 produced no objective response in 24 patients, although 11 had stable disease. The authors concluded that results so far were encouraging, but that ongoing trials will determine whether these therapies benefit patients. The article does not discuss asbestos.

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: Review of clinical trials and preclinical (laboratory and animal) research on mesothelin-targeted cancer treatments
• Who was studied: Published and ongoing studies of treatments for patients with mesothelin-expressing cancers, including mesothelioma and ovarian, pancreatic and lung cancers. The authors studied no new patients.
• Main results:
  • Citing earlier studies, the review reported that mesothelin is highly expressed in epithelial mesotheliomas (100% of cases) and in lung (50%), ovarian (70%) and pancreatic/biliary (100%) adenocarcinomas
  • A cited phase I trial gave SS1P alone by bolus infusion to 34 patients; it was one of two single-agent SS1P trials. Of 33 evaluable patients, 4 had minor responses and 10 had progressive disease. The text reports 19 with disease stabilization, while Table 1 reports 18 with stable disease for the same trial.
  • A cited ongoing trial combined SS1P with pemetrexed and cisplatin in malignant pleural mesothelioma. Of 14 evaluable patients, 7 had a partial response, 3 had stable disease and 4 had progressive disease. At the maximum tolerated dose, 5 of 7 evaluable patients had a partial response.
  • A cited phase I trial gave the antibody MORAb-009 to 24 patients (13 with mesothelioma, 7 with pancreatic cancer, 4 with ovarian cancer). No objective response was noted, although 11 patients had stable disease.
  • A cited phase I trial gave the vaccine CRS-207 to 17 patients. No objective antitumor response was observed, but a mesothelin-specific T-cell response was observed in 5 of 10 patients tested.
• The authors' conclusion: The authors concluded that trials of an anti-mesothelin immunotoxin, an antibody and a vaccine had shown encouraging activity, without untoward toxicity from targeting normal mesothelial cells. They added that ongoing trials will determine whether mesothelin-targeted therapies benefit patients.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelin, Clinical Trial, Malignant Mesothelioma, Lung Adenocarcinoma, Monoclonal Antibody.

Related studies

• Anti-Mesothelin Recombinant Immunotoxin Therapy for Colorectal Cancer — A. Cerise, T.K. Bera, et al. (2019)
• Microspheres targeted with a mesothelin antibody and loaded with doxorubicin reduce tumor volume of human mesotheliomas in xenografts — S.L. Macura, J.L. Steinbacher, et al. (2013)
• Mesothelin-Targeted CARs: Driving T Cells to Solid Tumors — A. Morello, M. Sadelain, et al. (2016)
• Mesothelin as a target for chimeric antigen receptor-modified T cells as anticancer therapy — M. O'Hara, C. Stashwick, et al. (2016)
• Mesothelin Immunotherapy for Cancer: Ready for Prime Time? — R. Hassan, A. Thomas, et al. (2016)
• Anetumab ravtansine: a novel mesothelin-targeting antibody-drug conjugate cures tumors with heterogeneous target expression favored by bystander effect — S. Golfier, C. Kopitz, et al. (2014)

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