Dose-related comparison of antibody-dependent cellular cytotoxicity with chimeric and native murine monoclonal antibody 17-1A. Improved cytolysis of pancreatic cancer cells with chimeric 17-1A.
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.
Haga
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Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198.
Sivinski
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Woo
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Tempero
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MA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity; D000954:Antigens, Surface / Q000032:analysis; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D051379:Mice; D010190:Pancreatic Neoplasms / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins