Expression of MAGE tumor rejection antigen on lung cancer and application for cancer vaccine

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(1) Peripheral blood mononuclear cells (PBMC) from lung cancer patients had been stimulared with GST-MAGE-1 or-4 fusion protein. However, we could not induct specific CTL against MAGE antigens. In the other hand, it had been possible to induce specific CTLs against MART-1 peptide restricted in HLA-A2 by the stimulation with this peptide in vitro (Sugita et al., Int. Immunol., 8 (5), 1996). (2) The MAGE genes are frequently expressed in many different cancers, but are not expressed in normal cells or normal tissues other than testis and placenta. Biological roles of proteins of MAGE family remained to be investigated. The expression of MAGE-1 or MAGE-4 protein in the testicular cells was studied immunohistochemically with the antibodies to the recombinant MAGE-1 or MAGE-4 protein. Both proteins were identified in the nucleus and cytoplasm of spermatogonia and in primary spermatocytes but not in spermatids or Sertoli's cells. Therefore, MAGE proteins are normal tissue antigens compartmen … More talized in particular testicular cells playing an important role in the early phase of the spermatogenesis (Takahashi et al, Cancer Res., 55,1995). (3) An enzyme-linked immunosorbent assay (ELISA) was established for measuring cellular MAGE-4 protein expressed on human tumor cells using a monoclonal antibody and polyclonal Ab to recombinant MAGE-4b protein (Shichijo et al., J Immunol. Method, 186,1995). (4) We investigated the level of MAGE-4 protein in sera of patients with primary lung cancer to understand the biological roles of the MAGE proteins. MAGE-4 protein was detected as a non-degraded from in both the supernatant of a MAGE-4^+ tumor cell line and in a patient's serum. Surum level of the MAGE-4 protein in lung cancer patients (n=100, mean=1.17ng/ml) was significantly higher than that in either patients with benign pulmonary diseases (n=80,033ng/ml) or healthy donors (n=68,032ng/ml). It was higher than the cutoff level (1.15ng/ml) in 34 of 100 cancer patients, but not in anyone in the other groups (Shichijo et al., JJCR,in press, 1997). (5) HLA class lrestriction and tumor specificity of cytotoxicity in the IL-2-activated tumor-infiltrating lymphocytes from 16 patients with non-small cell lung cancer were investigated. Six HLA class l-restricted and tumor-specific CTL lines were established : (i) HLA A2-restricted and adenocarcinoma-specific CTLs in three patients with adenocarcinoma, (ii) HLA-A3101-and A3302-restricted and adenocarcinoma-specific CTLs in an HLA-A3101/3302+patients with adenocarcinoma, and (iii) HLA-A3302-restricted CTLs and (iv) HLA-A2402-restricted CTLs recognizing tumors with different types of histology in an HLA-A3302+patients with adenocarcinoma and HLA-A2402 patients with squamous cell carcinoma, respectively (Seki et al., Cell. Immunol., 175,1997). These results showed evidence of the existence of HLA class l-restricted and tumor-specific CTLs recognizing peptide antigens on HLA-A alleles of adenocarcinoma or SCC in tumor sites of a Less