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

C-erb B-2产物被认为是一种独特且有用的靶点，可用于过表达c-erb B-2基因的癌症的抗体治疗。构建了含c-erbB-2基因产物胞外区、人源可变区骨架残基和IgG1恒定域的人源化抗体，并将其与顺铂(CDDP)联合应用于荷瘤4-1和人胃癌ST-40的SCID小鼠体内，观察其抗肿瘤作用。该抗体的抗肿瘤作用与顺铂有协同作用。这种协同作用的确切潜在机制仍不清楚，尽管目前正在进行评估。初步发现，CDDP和抗体联合治疗的小鼠肿瘤中铂含量高于单纯CDDP治疗的小鼠。在依托泊苷和MMC与抗体联合治疗的小鼠中，也发现了这些协同或相加的作用。

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.