In vivo experimeted model for anticancer therapy using murine and humanized monoclonal antibodies

c-erbB-2产物被认为是针对过表达c-erbB-2基因的癌症进行抗体治疗的独特而有用的靶点。在体外和体内研究了人源化抗体对c-erbB-2基因产物rhu4D5细胞外结构域的抗肿瘤作用。Rhu4D5对过表达c-erbB-2的SK-BR-3细胞系的直接抗增殖活性不如小鼠mu4D5有效。携带过表达4-1人胃癌异种移植物抗肿瘤活性的c-erbB-2在SCID小鼠体内的治疗此外，rhu4D5显著增强了人外周血单个核细胞对4-1的细胞毒性，而mu4D5则没有。这些结果表明，rhu4D5在患者中的作用可能比临床前研究预测的要好。尾静脉注射4-1细胞可使小鼠在80天内死亡。rhu4D5对动物的威胁稍微延长了小鼠的生存时间，但没有mu4D5的水平。

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. In vitro and in vivo antitumor effects of a humanized antibody against the extracellular domain of the c-erbB-2 gene product, rhu4D5, were examined. Rhu4D5 was less effective than its murine counterpart, mu4D5, for the direct antiproliferative activity against the c-erbB-2 overexpressing SK-BR-3 cell line. In vivo treatment of SCID mice carrying the c-erbB-2 overexpressing 4-1ST human gastric carcinoma xanograft anti-tumor activity. Furthemore, cytotoxicity of human peripheral blood mononuclear cells against 4-1ST was signnificantly augmented with rhu4D5, but not with mu4D5.These results indicate that rhu4D5 might be better in patients than predicted from preclinical studies.Injection of 4-1ST cells into the tail vein resulted in death of the mice within 80 days. Threatment of animals with rhu4D5 prolonged murine survival time slightly but not the level with mu4D5.