Cancer antigen profiling for malignant pleural mesothelioma immunotherapy: expression and coexpression of mesothelin, cancer antigen 125, and Wilms tumor 1

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// Takashi Eguchi 1, 2 , Kyuichi Kadota 1, 3, 4 , Marissa Mayor 1 , Marjorie G. Zauderer 5 , Andreas Rimner 6 , Valerie W. Rusch 1 , William D. Travis 3 , Michel Sadelain 7 and Prasad S. Adusumilli 1, 7 1 Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA 2 Division of Thoracic Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan 3 Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA 4 Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan 5 Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA 6 Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA 7 Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA Correspondence to: Prasad S. Adusumilli, email: adusumip@mskcc.org Keywords: mesothelin, CA125, WT1, mesothelioma, chimeric antigen receptor Received: May 10, 2017     Accepted: August 15, 2017     Published: September 12, 2017 ABSTRACT Background: To develop cancer antigen-targeted immunotherapeutic strategies for malignant pleural mesothelioma (MPM), we investigated the individual and coexpressions of the cancer-associated antigens mesothelin (MSLN), cancer antigen 125 (CA125), and Wilms tumor 1 (WT1) in both epithelioid and non-epithelioid MPM. Methods: All available hematoxylin and eosin-stained slides from patients who were diagnosed with MPM (1989-2010) were reviewed. We constructed tissue microarrays from 283 patients (epithelioid = 234; non-epithelioid = 49). Intensity and distribution for each antigen were assessed by immunohistochemistry. Results: Positive expression of MSLN, CA125, and WT1 were demonstrated in 93%, 75%, and 97% of epithelioid MPM cases, and 57%, 33%, and 98% of non-epithelioid MPM cases, respectively. Triple- and double-positive antigen coexpressions were demonstrated in 72% and 23% of epithelioid MPM cases and 29% and 33% of non-epithelioid MPM cases, respectively. Complete absence of expression for all three antigens was demonstrated in <2% of MPM cases. More than two-thirds of MPM cases had ≥50% distribution of MSLN-positive cells and, among the remaining third, half had ≥50% distribution of WT1-positive cells. CA125/MSLN coexpression was observed in more than two-thirds of epithelioid MPM cases and one-third of non-epithelioid MPM cases. Conclusion: A limited number of cancer-associated antigens can target almost all MPM tumors for immunotherapy.