ANTI-TUMOR IMMUNOTHERAPY WITH A HUMANIZED MONOCLONAL ANTIBODY AGAINST HUMAN PROTO-ONCOGENE PRODUCT

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。研究了一种人源化抗体对c-erbB-2基因产物rhu4D5细胞外结构域的体外和体内抗肿瘤作用。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。用rhu4D5对携带过表达4-1人胃癌异种移植物c-erbB-2的SCID小鼠进行体内处理，发现重组蛋白具有很强的抗肿瘤活性。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。有必要进行临床试验。

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 anti-tumor 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 xenograft with rhu4D5 revealed that the recombinant protein had potent anti-tumor activity. Furthermore, cytotoxicity of human peripheral blood mononuclear cells against 4-1ST was significantly augmented with rhu4D5, but not with mu4D5.These results indicate that rhu4D5 mmight be better in patients than predicted from preclinical studies. A clinical trial would be warranted.