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Review
. 2016 Dec;34(34):4171-4179.
doi: 10.1200/JCO.2016.68.3672. Epub 2016 Oct 31.

Mesothelin Immunotherapy for Cancer: Ready for Prime Time?

Raffit Hassan  1 , Anish Thomas  1 , Christine Alewine  1 , Dung T Le  1 , Elizabeth M Jaffee  1 , Ira Pastan  1
Affiliations
Review

Mesothelin Immunotherapy for Cancer: Ready for Prime Time?

Raffit Hassan et al. J Clin Oncol. 2016 Dec.

Abstract

Mesothelin is a tumor antigen that is highly expressed in many human cancers, including malignant mesothelioma and pancreatic, ovarian, and lung adenocarcinomas. It is an attractive target for cancer immunotherapy because its normal expression is limited to mesothelial cells, which are dispensable. Several antibody-based therapeutic agents as well as vaccine and T-cell therapies directed at mesothelin are undergoing clinical evaluation. These include antimesothelin immunotoxins (SS1P, RG7787/LMB-100), chimeric antimesothelin antibody (amatuximab), mesothelin-directed antibody drug conjugates (anetumab ravtansine, DMOT4039A, BMS-986148), live attenuated Listeria monocytogenes-expressing mesothelin (CRS-207, JNJ-64041757), and chimeric antigen receptor T-cell therapies. Two antimesothelin agents are currently in multicenter clinical registration trials for malignant mesothelioma: amatuximab in the first-line setting and anetumab ravtansine as second-line therapy. Phase II randomized clinical trials of CRS-207 as a boosting agent and in combination with immune checkpoint inhibition for pancreatic cancer are nearing completion. These ongoing studies will define the utility of mesothelin immunotherapy for treating cancer.

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Conflict of interest statement

Authors’ disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
Approaches used to target MSLN in clinical trials. APC, antigen-presenting cell; CAR, chimeric antigen receptor; DM4, ravtansine; mAb, monoclonal antibody; PE, pseudomonas exotoxin.
See this image and copyright information in PMC

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