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AN ENGINEERED AND ASSEMBLED FUSION PROTEIN OF ANTITUMOR ANTIBIOTIC LIDAMYCIN AND scFv ANTIBODY DIRECTED AGAINST TYPE IV COLLAGENASE
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- Author:
- No author available
- Journal Title:
- ACTA PHARMACEUTICA SINICA
- Issue:
- 7
- DOI:
- 10.3321/j.issn:0513-4870.2000.07.003
- Key Word:
- Fv单链抗体;免疫偶联物;IV型胶原酶;肿瘤侵袭;抗肿瘤抗生素;力达霉素
Abstract： 目的以IV型胶原酶为靶点,研制兼具有抗肿瘤侵袭转移和强烈杀伤肿瘤细胞的新型单抗导向药物.方法力达霉素(LDM)分子由力达蛋白(LDP)和力达发色团(LDC)两部分组成.从基因工程转化菌中提取融合蛋白(LDP-Fv)并与LDC 组装重建,制备高效抗癌抗生素力达霉素与单链抗体的组装融合蛋白(LDM-Fv).通过ELISA、酶谱分析、Boyden 小室体外侵袭实验及克隆形成测定,观察其生物学活性.结果 LDM-Fv能特异性与肿瘤细胞的IV型胶原酶结合并抑制其活性,LDP-Fv有阻断肿瘤细胞侵袭的能力,但无细胞毒性,加入LDC制成的组装融合蛋白LDM-Fv对肿瘤细胞有强烈的杀伤作用,并明显强于丝裂霉素和阿霉素.结论 LDM-Fv可能成为一种新型高效、小型化抗肿瘤导向药物.
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