A MOUSE HUMAN CHIMERIC ANTI-(GANGLIOSIDE-GD3) ANTIBODY WITH ENHANCED ANTITUMOR ACTIVITIES

Ganglioside GD3, which is one of the major gangliosides expressed on t he cell surface of human tumors of neuroectodermal origin has been foc used on as a target molecule for passive immunotherapy. We have cloned the cDNA encoding the immunoglobulin light and heavy chains of an ant i-GD3 monoclonal antibody KM641 (murine IgG3, kappa), and constructed the chimeric genes by linking the cDNA fragments of the murine light a nd heavy variable regions to cDNA fragments of the human kappa and gam ma1 constant regions, respectively. The transfer of these cDNA constru cts into SP2/0 mouse myeloma cells resulted in the production of the c himeric antibody, designated KM871, that retained specific binding act ivity to GD3. Indirect immunofluorescence revealed the same staining p attern for chimeric KM871 and the mouse counterpart KM641 on GD3-expre ssing melanoma cells. When human serum and human peripheral blood mono nuclear cells were used as effectors in complement-mediated cytotoxici ty and antibody-dependent cell-mediated cytotoxicity respectively, the chimeric KM871 was more effective in killing GD3-expressing tumor cel ls than was the mouse counterpart KM641. Intravenous injection of chim eric KM871 markedly suppressed tumor growth in nude mice. The chimeric KM871, having enhanced antitumor activities and less immunogenicity t han the mouse counterpart, would be a useful agent for passive immunot herapy of human cancer.