Polyclonal anti-idiotypic antibodies mimicking the small cell lung carcinoma antigen cluster-5A interact with a panel of antibodies and induce specific immune response in animals

Abstract

Polyclonal anti-idiotypic antibodies (ab2) were generated by immunising goats with the murine IgG2a monoclonal antibody SWA20 which recognises the SCLC antigen cluster-5A, a tumour-associated sialoglycoprotein. Ab2 was shown to bind specifically to antibody SWA20, but not to isotype matched control antibodies. Pre-incubation with ab2 completely inhibited target cell binding of antibody SWA20 and of four other antibodies to cluster-5A antigen, while no effect was seen with antibodies to cluster-1 and cluster-w4 antigen. By these criteria the ab2 population consists of antibodies resembling in their reactivity pattern the cluster-5A antigen. Ab2 was used for immunisation of rabbits and two strains of mice; control animals received PBS or nonspecific goat IgG. Anti-anti-idiotype sera (ab3) were analysed in a series of radioimmunoassays for reactivity with goat IgG and reactivity with ab2. After blocking the nonspecific anti-goat response, ab3 could be shown to bind specifically to ab2 idiotype. As examined by an indirect cell ELISA with fixed cells, two out of six ab3 sera showed significantly higher binding ratios to antigen-positive SW2 cells as compared to antigen negative control cells. These findings indicate that the goat anti-SWA20 idiotype antibodies functionally represent the SCLC antigen cluster-5A and therefore may have potential for modulating the anti-tumour response through idiotypic network interactions.