Mouse monoclonal antibodies for experimental immunotherapy promotes killing of tumor cells

Abstract

Monoclonal antibodies (MAbs) produced against a human colon adenocarcinoma cell line, Colo-205, were tested in antibody-dependent macrophage-mediated cytotoxicity (ADMMC) assays. The antibodies C163, C215, C245 (IgG_2a isotype); C1S1, C239, C241, C242 (IgG₁); C152 (IgG_2b); and C50 (IgM) were evaluated for their ability to promote killing of Colo-205 cells by thioglycollate-elicited peritoneal mouse macrophages. The concentrations of antibodies tested in ADMMC assays ranged from 1.0 ng/ml to 100 μg/ml, and the concentration at which 50% of tumor cells were lysed was used to characterize each antibody. Antibodies of the IgG_2a isotype promoted the strongest macrophage-mediated tumor cell lysis effects in vitro. MAbs C215, C163, and C245 were also tested in nude mice which had been inoculated with Colo-205 cells. Tumor suppression was observed in mice injected with MAbs, supporting our ADMMC findings in vitro. Animals treated with MAbs had fewer and smaller tumors, and longer periods of latency between the inoculation of tumor cells and development of tumors, compared to mice sham-treated with PBS. However, in a study of established tumors, C215 antibody did not suppress tumor growth. Serum collected from MAb-treated mice promoted lysis of Colo-205 cells in ADMMC assays while serum from sham-treated mice did not.