Cytotoxic activity of the recombinant anti-mesothelin immunotoxin, SS1(dsFv)PE38, towards tumor cell lines established from ascites of patients with peritoneal mesotheliomas.
BACKGROUND
Mesothelin, a cell surface glycoprotein, is an attractive candidate for targeted therapy given its overexpression, as detected by immunohistochemistry, in mesotheliomas. The goal of this study was to evaluate mesothelin expression in fresh tumor cells obtained from ascites of patients with peritoneal mesothelioma, as well as to determine the sensitivity of these cells to an immunotoxin targeting mesothelin.


METHODS
Tumor cells were evaluated for mesothelin expression by flow cytometry using the murine anti-mesothelin monoclonal antibody K1. The sensitivity of these tumor cells to SS1(dsFv)PE38, an immunotoxin consisting of the anti-mesothelin Fv linked to a mutated Pseudomonas exotoxin, was evaluated using a cell proliferation assay.


RESULTS
Of the 7 tumor cell lines established from ascites of 12 patients with peritoneal mesothelioma, 6 expressed mesothelin while one cell line did not. Cell lines that expressed mesothelin were very sensitive to SS1(dsFv)PE38 with IC50s ranging between 0.08-3.9 ng/ml, while the cell line that was mesothelin-negative was resistant to SS1(dsFv)PE38.


CONCLUSIONS
High expression of mesothelin is seen on tumor cells of patients with peritoneal mesothelioma and correlates with sensitivity to SS1(dsFv)PE38. Clinical studies of SS1(dsFv)PE38 in patients with peritoneal mesotheliomas are ongoing.
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Qian
Q
Li
Claire F
CF
Verschraegen
John
J
Mendoza
Raffit
R
Hassan
D000911:Antibodies, Monoclonal / Q000276:immunology; D001201:Ascites / Q000473:pathology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D058851:GPI-Linked Proteins; D006801:Humans; D000922:Immunotoxins / Q000276:immunology / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology*; D000090204:Mesothelin; D008654:Mesothelioma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D000911:Antibodies, Monoclonal; D058851:GPI-Linked Proteins; D000922:Immunotoxins; D008562:Membrane Glycoproteins; C474515:SS1(dsFv)PE38; D000090204:Mesothelin