SYNERGISTIC EFFECTS OF HUMANIZED ANTI-c-erbB-2 MONOCLONAL ANTIBODY WITH CHEMOTHERAPEUTIC AGENTS

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The c-erbB-2 product is thought to be an unique and useful target for antibody therapy of cancers overexpressing the c-erbB-2 gene. A humanized antibody which contained only the antigen-binding loops from a murine monoclonal antibody against the extracellular domain of the c-erbB-2 gene product, human variable region framework residues and IgG1 constant domains was constructed.In vivo anti-tumor effects of the humanized anti-c-erbB-2 monoclonal antibody with CDDP were examined using SCID mice bearing 4-1ST and St-40 of c-erbB-2 positive human gastric cancer xenografis. Anti-tumor effects of the antibody were found to be synergistic with CDDP. The precise underlying mechanism for this synergistic interaction remains unknown, though it is currently being evaluated. Preliminary, platinum contents of the tumors were higher in the mice treated with CDDP and the antibody than those only with CDDP. These synergistic or additive effects were also found in the mice treated with etoposide and MMC in conjunction with the antibody.