title: Major cancer regressions in mesothelioma after treatment with an anti-mesothelin immunotoxin and immune suppression.
abstract: 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.
authors.affiliation: Laboratory of Molecular Biology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
authors.forename: Raffit
authors.initials: R
authors.lastname: Hassan
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Miller
authors.forename: Elad
authors.initials: E
authors.lastname: Sharon
authors.forename: Anish
authors.initials: A
authors.lastname: Thomas
authors.forename: James C
authors.initials: JC
authors.lastname: Reynolds
authors.forename: Alexander
authors.initials: A
authors.lastname: Ling
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kreitman
authors.forename: Markku M
authors.initials: MM
authors.lastname: Miettinen
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Fowler
authors.forename: Ira
authors.initials: I
authors.lastname: Pastan
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001772:Blood Cell Count; D005260:Female; D058851:GPI-Linked Proteins / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy; D053208:Kaplan-Meier Estimate; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D008297:Male; D000090204:Mesothelin; D008654:Mesothelioma / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D010534:Peritoneal Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D011859:Radiography; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D058851:GPI-Linked Proteins; C474515:SS1(dsFv)PE38; D000090204:Mesothelin