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

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Abstract
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 antiidiotype 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.