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.