Development of cancer immunotherapy using antibody specific for tumor antigens recognized by tumor-infiltration B cells

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Recent progress of immunotherapy by antibody have provided us hope of identification of target antigen as a novel immunotherapy. We previously demonstrated that tumor-infiltrating B cells recognized tumor antigens and produced antibodies against them by a using modified SEREX method. In the present study, we have identified tumor-associated antigens in two lung cancer patients and analyzed the usefulness of antigens for tumor marker and immunotherapy. In patient 1 (G603), one of identified antigens was revealed to be MAGE-B2. In the immuno-monitoring of the patient's sera, high antibody titer against MAGE-B2 was observed before operation and the titer decreased after resection of the primary tumor. It was elevated again at the time of adrenal metastasis, but then decreased after resection, indicating that anti-MAGE-B2 antibody could be used as tumor markers for the patient. In patient2, 22 distinct antigens were isolated. Of these antigens, Protein X was highly expressed in 5 out of 9 lung cancer cell lines by RT-PCR. Moreover, Protein X was overexpressed in 9 out of 15 lung cancer tissues compared with corresponding normal lung tissues. Polyclonal antibody against Protein X was generated and was analyzed for localization of antigens and for anti-tumor activity. Flow cytometory showed that Protein X expressed in the cell surface of tumor cells with high expression of this antigen. Immunohistochemical analysis revealed that Protein X was expressed in cell membrane of tumor cells in 7 out of 28 tumor tissues. Tumor implanted in SCID mouse regressed by the inoculation of anti-Protein X antibody. In vitro analysis, anti-tumor acticity was mediated by CDC mechanism. These result indicated that these antigens recognized by TIB could be usefull for clinical diagnosis as a tumor marker and for clinical application of antibody-mediated immunotherapy.