RT Journal Article SR Electronic T1 Major Cancer Regressions in Mesothelioma After Treatment with an Anti-Mesothelin Immunotoxin and Immune Suppression JF Science Translational Medicine FD American Association for the Advancement of Science SP 208ra147 OP 208ra147 DO 10.1126/scitranslmed.3006941 VO 5 IS 208 A1 Hassan, Raffit A1 Miller, Andrew C. A1 Sharon, Elad A1 Thomas, Anish A1 Reynolds, James C. A1 Ling, Alexander A1 Kreitman, Robert J. A1 Miettinen, Markku M. A1 Steinberg, Seth M. A1 Fowler, Daniel H. A1 Pastan, Ira YR 2013 UL http://stm.sciencemag.org/content/5/208/208ra147.abstract AB Immunotoxins are potent anticancer agents with an unusual mechanism of action: inhibition of protein synthesis resulting in apoptotic cell death. Immunotoxins have produced many durable complete responses in refractory hairy cell leukemia, where patients rarely form antibodies to the bacterial toxin component of the immunotoxin. Patients with mesothelioma, however, have normal immune systems and form antibodies after one cycle, and tumor responses to the immunotoxin have not been observed in this disease. We describe the results of a trial in which major antitumor responses were seen in patients with advanced mesothelioma who received the anti-mesothelin immunotoxin SS1P, together with pentostatin and cyclophosphamide, to deplete T and B cells. Of 10 patients with chemotherapy-refractory mesothelioma, 3 have had major tumor regressions with 2 ongoing at 15 months, and 2 others responded to chemotherapy after discontinuing immunotoxin therapy. Antibody formation was markedly delayed, allowing more SS1P cycles to be given, but this alone does not appear to account for the marked antitumor activity observed.