Monoclonal anti-idiotypic antibody mimicking a tumor-associated sialoglycoprotein antigen induces humoral immune response against human small-cell lung carcinoma

We have previously described the tumor-associated sialoglycoprotein antigen sGP90-135 defined by the murine LAM8 MAb. The antigen is characterized by strong membrane expression in a proportion of small-cell carcinomas of the lung, but little or no expression on normal tissues of epithelial or neural origin or on blood cells. With the aim of obtaining anti-idiotypic antibodies which might be useful as surrogates for sGP90-135 in vaccination studies, LOU rats were immunized with LAM8 MAb and their spleen cells fused with Y3 rat myeloma cells. The LY8-229 hybrid was selected by an anti-idiotype competition radioimmunoassay on antigen-positive target cells. LY8-229 was shown to be a rat IgG1 with high specificity for LAM8 combining site. Solubilized small-cell carcinoma extract, as well as antibody SEN16, which recognizes the same tumor-associated antigen sGP90-135, selectively inhibited 125I-LY8-229 binding to LAM8. Serum from BALB/c mice and DA rats immunized with anti-idiotypic antibody LY8-229 showed reactivity with antigen-positive target cell lines, but not with antigen-negative control cell lines. The induction of a specific immune response in 2 different species by the anti-idiotypic antibody LY8-229 suggests that LY8-229 bears the internal image of the antigen sGP90-135 and that it might be a candidate for immunotherapy trials in cancer patients.