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BR96-阿霉素免疫偶联物对异种移植人癌的治疗作用

Cure of xenografted human carcinomas by BR96-doxorubicin immunoconjugates.

作者信息

Trail P A, Willner D, Lasch S J, Henderson A J, Hofstead S, Casazza A M, Firestone R A, Hellström I, Hellström K E

机构信息

Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543.

出版信息

Science. 1993 Jul 9;261(5118):212-5. doi: 10.1126/science.8327892.

Abstract

Immunoconjugates (BR96-DOX) were prepared between chimeric monoclonal antibody BR96 and the anticancer drug doxorubicin. The monoclonal antibody binds an antigen related to Lewis Y that is abundantly expressed at the surface of cells from many human carcinomas; it has a high degree of tumor selectivity and is internalized after binding. BR96-DOX induced complete regressions and cures of xenografted human lung, breast, and colon carcinomas growing subcutaneously in athymic mice and cured 70 percent of mice bearing extensive metastases of a human lung carcinoma. Also, BR96-DOX cured 94 percent of athymic rats with subcutaneous human lung carcinoma, even though the rats, like humans and in contrast to mice, expressed the BR96 target antigen in normal tissues.

摘要

在嵌合单克隆抗体BR96与抗癌药物阿霉素之间制备了免疫缀合物(BR96-DOX)。该单克隆抗体可结合与Lewis Y相关的抗原,这种抗原在许多人类癌细胞表面大量表达;它具有高度的肿瘤选择性,结合后会被内化。BR96-DOX可使无胸腺小鼠皮下生长的人肺癌、乳腺癌和结肠癌异种移植物完全消退并治愈,还能治愈70%患有广泛人肺癌转移的小鼠。此外,BR96-DOX治愈了94%患有皮下人肺癌的无胸腺大鼠,尽管这些大鼠与人类一样,与小鼠不同,在正常组织中表达BR96靶抗原。

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