Dose-related comparison of antibody-dependent cellular cytotoxicity with chimeric and native murine monoclonal antibody 17-1A

Abstract

Chimeric 17-1A antibody (IgG1 kappa) was constructed by linking variable region genes of murine monoclonal antibody 17-1A with genes for human kappa light chain and gamma 1 heavy-chain constant regions. This study was undertaken to compare in vitro antibody-dependent cellular cytotoxicity (ADCC) between the chimeric 17-1A (IgG1 kappa) and native murine 17-1A antibody (IgG2a kappa) with human peripheral blood mononuclear cells (PBMNC) against 7 human tumor (1 colon, 6 pancreas) cell lines. ADCC activity was measured by chromium-release assay. When freshly-isolated PBMNC from healthy donors were used for effector cells, significantly higher ADCC activity of chimeric antibody compared to murine antibody at optimal antibody dose (10 micrograms/mL) and lower doses (to 0.6 micrograms/mL) was observed against tumor cells with relatively high 17-1A expression. This high ADCC activity of the chimeric antibody persisted even when freshly-isolated monocyte-depleted PBMNC was used. When interleukin-2 activated PBMNC were used, comparable increases in ADCC were observed with both chimeric and murine antibody. These results suggest that chimeric 17-1A antibody is a more effective mediator of in vitro ADCC activity with human freshly-isolated PBMNC than the native murine antibody and this may be a better choice for clinical cancer trials evaluating possible immunotherapy with monoclonal antibody.