In vitro and in vivo anti-tumour effects of a humanised monoclonal antibody against c-erbB-2 product
In vitro and in vivo anti-tumour effects of a humanised monoclonal antibody against c-erbB-2 product
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DOI：
10.1038/bjc.1996.259
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发表时间：
1996-06-01
影响因子：
8.8
通讯作者：
Mitomi, T
中科院分区：
文献类型：
--
作者：
Tokuda, Y;Ohnishi, Y;Mitomi, T
c-erbB-2产物被认为是用于过表达c-erbB-2基因的癌症的抗体治疗的独特且有用的靶标。在体外和体内抗肿瘤作用的人源化抗体对c-erbB-2基因产物，rhu 4D 5的细胞外结构域进行了检查。Rhu 4D 5对c-erbB-2过表达的SK-BR-3细胞系的直接抗增殖活性不如其鼠对应物mu 4D 5有效。rhu 4D 5对携带c-erbB-2过表达的4-1ST人胃癌异种移植物的严重联合免疫缺陷（SCID）小鼠的体内治疗显示，重组蛋白具有有效的抗肿瘤活性。此外，对4-1ST的人外周血单核细胞的细胞毒性显着增强与rhu 4D 5，但不与mu 4D 5。这些结果表明rhu 4D 5在患者中的表现可能比临床前研究预测的更好。
The c-erbB-2 product is thought to be a unique and useful target for antibody therapy of cancers overexpressing the c-erbB-2 gene. In vitro and in vivo anti-tumour effects of a humanised 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 severe combined immunodeficient (SCID) mice carrying the c-erbB-2-overexpressing 4-1ST human gastric carcinoma xenograft with rhu4D5 revealed that the recombinant protein had potent anti-tumour 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 might perform better in patients than predicted from preclinical studies.