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

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。检测了针对c-erbB-2基因产物胞外区的人源化抗体rhu4D5的体内外抗肿瘤作用。Rhu4D5对高表达c-erbB-2的SK-BR-3细胞株的直接抗增殖作用弱于其相应的小鼠模型mu4D5。用rhu4D5对携带c-erbB-2高表达的人胃癌移植瘤的SCID小鼠进行体内治疗，结果表明重组蛋白具有较强的抗肿瘤活性。此外，rhu4D5可显著增强人外周血单个核细胞对4-1的细胞毒作用，但mu4D5不能。这些结果表明，rhu4D5对患者的疗效可能好于临床前研究的预测。临床试验将是必要的。

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.