Malignant mesothelioma associated antigens recognized by tumor infiltrating B cells. -usefulness of antibody titer to the antigens -

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Malignant pleural mesothelioma is difficult to be diagnosed at early stage and universally accepted therapy has not been established. In this study, we tried to obtain tumor specific antibody derived from tumor infiltrated B lymphocytes (TIB) in malignant mesothelioma by using xenotransplanted SCID mice model, and applied TIB-produced IgG to serological identification of antigens by recombinant expression cloning method (SEREX).Surgical specimens from 5 patients with malignant mesothelioma have been tried to establish tumor cell lines, and also these mesothelioma tissues were engrafted subcutaneously in SCID mice and blood samples were obtained every 2 weeks after xenotransplantation. Two mesothelioma cell lines have been established (K921MS0 and L324MSO). cDNA library was constructed from a tumor cell line (K921MS0) of malignant mesothelioma. Immunoscreening of the library was performed using the serum from SCID mice transplanted with mesothelioma tissues. Immuno-reactive cDNA clones … More were subcloned, and analyzed using database for homology search. Antibodies titers against the identified antigens were analyzed in sera of patients with malignant mesothelioma.Immunohistochemical staining revealed that B lymphocytes infiltrated in tumor tissues. In all SCID mouse serum, human IgG antibody could be detected (ranged from 134 to 24000μg/ml). By using antibodies derived from TIB, 11 antigens were identified. Six antigens showed over expression for malignant mesothelioma. Antibodies against the 6 antigens could be detected not only in serum of SCID mouse but also in sera of mesothelioma patients. Among them, antibody against Gene-X was detected in 7 out of 12 mesothelioma patients, and antibody against Thrombospondin-2 was detected in 11 out of 12 mesothelioma patients.Our results suggest that the B cells infiltrated in the tumor tissues have been sensitized and produced antibody against tumor associate antigens. Among the SEREX defined antigens, 2 antigens (Gene-X and Thrombosponddin-2) were overexpressed in malignant mesothelioma, and antibodies against them could be detected in higher proportion of mesothelioma patients than normal healthy persons. These two antigens could be used as tumor markers for diagnosis of patients with malignant mesothelioma. Less