Lu Z R, Shiah J G, Kopecková P, Kopecek J
Department of Pharmaceutics and Pharmaceutical Chemistry/CCCD, 30 S 2000 E Rm 301, University of Utah, Salt Lake City, UT 84112, USA.
J Control Release. 2001 Jul 6;74(1-3):263-8. doi: 10.1016/s0168-3659(01)00332-7.
A new polymerizable antibody Fab' fragment with a PEG spacer (MA-PEG-Fab') was prepared from OV-TL 16 antibody, specific against the OA-3 antigen expressed on most human ovarian carcinomas. The MA-PEG-Fab' possessed a higher reactivity in the copolymerization with N-(2-hydroxypropyl)methacrylamide (HPMA) than the polymerizable Fab' fragment MA-Fab' with a short spacer. The MA-PEG-Fab' was copolymerized with HPMA and MA-Gly-Phe-Leu-Gly-Mce(6) producing an Fab' targeted HPMA copolymer-Mce(6) conjugate. The number and weight average molecular weights of the copolymer were 164000 and 271000 Da, respectively. About two MA-PEG-Fab' fragments per chain were incorporated in the copolymer conjugates. Preliminary in vivo antitumor studies indicated that the Fab' targeted conjugates showed a higher efficacy of tumor growth inhibition in nude mice than the non-targeted conjugate.
从OV-TL 16抗体制备了一种带有聚乙二醇（PEG）间隔基的新型可聚合抗体Fab'片段（MA-PEG-Fab'），该抗体对大多数人卵巢癌上表达的OA-3抗原具有特异性。与具有短间隔基的可聚合Fab'片段MA-Fab'相比，MA-PEG-Fab'在与N-（2-羟丙基）甲基丙烯酰胺（HPMA）共聚时具有更高的反应活性。MA-PEG-Fab'与HPMA和MA-Gly-Phe-Leu-Gly-Mce(6)共聚，生成一种Fab'靶向的HPMA共聚物-Mce(6)缀合物。该共聚物的数均分子量和重均分子量分别为164000 Da和271000 Da。每条链约有两个MA-PEG-Fab'片段掺入共聚物缀合物中。初步的体内抗肿瘤研究表明，与非靶向缀合物相比，Fab'靶向缀合物在裸鼠中显示出更高的肿瘤生长抑制效果。
