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抗体靶向光解:使用修饰的葡聚糖载体将四价锡二氢卟吩e6与单克隆抗体共价结合的体外研究。

Antibody-targeted photolysis: in vitro studies with Sn(IV) chlorin e6 covalently bound to monoclonal antibodies using a modified dextran carrier.

作者信息

Rakestraw S L, Tompkins R G, Yarmush M L

机构信息

Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ 08855-0909.

出版信息

Proc Natl Acad Sci U S A. 1990 Jun;87(11):4217-21. doi: 10.1073/pnas.87.11.4217.

Abstract

A monoclonal antibody-dextran-Sn(IV) chlorin e6 immunoconjugate was prepared by a technique involving the site-specific covalent modification of the monoclonal antibody oligosaccharide moiety. Dextran carriers were synthesized with a single chain-terminal hydrazide group, which was used as the coupling point between the carrier and the monoclonal antibody carbohydrate. Selective in vitro photolysis of SK-MEL-2 human malignant melanoma cells was accomplished using several conjugates prepared from anti-melanoma 2.1 (chromophore:antibody molar ratios, 6.8 and 11.2). Phototoxicity, as measured by clonogenic assay, was dependent on the delivered dose of 634-nm light and was observed only for conjugates that bound SK-MEL-2 cells. As judged by competitive inhibition radioimmunoassay, conjugates prepared in this fashion showed excellent retention of antigen binding activity relative to the unmodified antibody.

摘要

一种单克隆抗体 - 葡聚糖 - 四价锡二氢卟吩e6免疫缀合物是通过一种涉及单克隆抗体寡糖部分位点特异性共价修饰的技术制备的。合成了具有单链末端酰肼基团的葡聚糖载体,该基团用作载体与单克隆抗体碳水化合物之间的偶联点。使用由抗黑素瘤2.1制备的几种缀合物(发色团:抗体摩尔比为6.8和11.2)实现了对SK - MEL - 2人恶性黑色素瘤细胞的选择性体外光解。通过克隆形成试验测定的光毒性取决于634 nm光的递送剂量,并且仅在结合SK - MEL - 2细胞的缀合物中观察到。通过竞争性抑制放射免疫测定判断,以这种方式制备的缀合物相对于未修饰的抗体显示出优异的抗原结合活性保留。

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