Endogenous anti-tumor antibody responses in nude mice.

Abstract

Nude mice with xenografted human tumors is the most exploited animal model used to elucidate the efficacy of experimental radioimmunolocalization and radioimmunotherapy. These animals accept transplants and are generally considered immunologically inert with regard to cell-mediated and humoral immune responses against the tumors. Nude control mice and mice carrying human HeLa Hep-2 tumor xenografts were studied for appearance of endogenous antibodies following inoculation with tumor cells. The titers of these antibodies were investigated by isotype-specific enzyme-linked immunosorbent assay (ELISA) technologies, fluorescence-activated cell sorter analysis (FACS), BIAcore (Pharmacia Biosensor AB, Uppsala, Sweden) technology, and immunofluorescence. The HeLa Hep-2 cell line was found to be immunogenic in all investigated animals by means of ELISA, FACS, and BIAcore evaluations as well as by immunofluorescence against both tested antigens, placental alkaline phosphatase and cytokeratin 8. Predominantly immunoglobulin M antibodies were induced, but immunoglobulin G isotypes could also be identified. Sera from these tumor-bearing mice were used for immunohistochemistry of the tumor cells. The antibodies seemed to be of low affinity and may be displaced by high-affinity monoclonal antibodies used in radioimmunotargeting. Nude mice bearing tumor xenografts produce significant amounts of antibodies against these two human tumor-derived antigens. These endogenous antibodies may influence targeting of radiolabeled antibodies. They also have the potential to interfere with the pharmacokinetics of labeled or nonlabeled idiotypic antibodies during experimental immunolocalization.