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一种单克隆抗癌胚抗原抗体-蓖麻毒素A链缀合物对人癌胚抗原产生肿瘤细胞的作用。

Effect of a monoclonal anti-carcinoembryonic antigen antibody-ricin A-chain conjugate on human carcinoembryonic antigen-producing tumor cells.

作者信息

Watanabe Y, Miyazaki H, Osawa T

出版信息

J Pharmacobiodyn. 1984 Aug;7(8):593-603. doi: 10.1248/bpb1978.7.593.

Abstract

For the development of therapeutic agents that are coupled to tumor specific carriers, an artificial protein hybrid conjugate (immunotoxin) containing monoclonal anti-carcinoembryonic antigen (CEA) antibody which binds specifically to the cell surface of CEA-producing tumor cells and a toxic subunit of ricin (A-chain) was prepared. This conjugate exerted strong cytotoxicity specifically toward CEA-producing tumor cells in vitro. In vivo, it has anti-tumor effects on ascitic tumor cells, and on free tumor cells before the solid tumor has been established. However, for the established solid tumor, a significant decrease of tumor growth was not seen even after repeated intravenous administrations of the antibody-ricin A-chain conjugate. Furthermore, the conjugate was found to be stable in both mouse and human serum in vitro, but after intravenous injection, it was inactivated in vivo quickly.

摘要

为了开发与肿瘤特异性载体偶联的治疗剂,制备了一种人工蛋白质杂交偶联物(免疫毒素),其包含与产生癌胚抗原(CEA)的肿瘤细胞的细胞表面特异性结合的单克隆抗癌胚抗原(CEA)抗体和蓖麻毒素的毒性亚基(A链)。这种偶联物在体外对产生CEA的肿瘤细胞具有强烈的细胞毒性。在体内,它对腹水肿瘤细胞以及实体瘤形成前的游离肿瘤细胞具有抗肿瘤作用。然而,对于已形成的实体瘤,即使重复静脉注射抗体-蓖麻毒素A链偶联物后,也未观察到肿瘤生长的显著降低。此外,该偶联物在体外小鼠和人血清中均稳定,但静脉注射后,它在体内迅速失活。

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