| 力达霉素-单抗Fab'片段不同连接偶联物的抗肿瘤作用比较 |
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| 引用本文： | Feng Y,Shao RG,Dai Y,Li BW,He HW,Ren KH. 力达霉素-单抗Fab'片段不同连接偶联物的抗肿瘤作用比较[J]. 药学学报, 2010, 45(5): 571-575 |
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| 作者姓名： | Feng Y Shao RG Dai Y Li BW He HW Ren KH |
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| 作者单位： | 江苏大学基础医学与医学技术学院;中国医学科学院、北京协和医学院医药生物技术研究所; |
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| 基金项目： | 国家重点基础研究发展计划(973计划)资助项目(2009CB521807); 国家自然科学基金资助项目(30472107,30701031); 江苏大学高级专业人才科研启动基金资助项目(06jdg045) |
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| 摘 要： | 研究力达霉素与抗Ⅳ型胶原酶单抗的不同连接键的小型化免疫偶联物的抗肿瘤作用。制备长短链的二硫键以及硫醚键抗肿瘤抗生素力达霉素(LDM)与抗Ⅳ型胶原酶单抗3G11的Fab'片段连接的免疫偶联物,ELISA法测定偶联物的免疫活性,体外细胞克隆形成测定和体内荷瘤裸小鼠模型观察两种偶联物的抗肿瘤作用。体外研究显示,Fab'-LDM偶联物部分保留了抗Ⅳ型胶原酶单抗3G11对抗原的亲和力,硫醚键偶联物对体外培养的人纤维肉瘤HT-1080细胞的杀伤作用强于LDM和二硫键偶联物。实验结果显示,LDM等剂量条件下硫醚键偶联物Fab'-SSMPB-LDM和Fab'-SMBS-LDM组的抑瘤率分别为87.7%和78.0%,二硫键偶联物Fab'-SPDP-LDM和Fab'-LCSPDP-LDM组分别为74.8%和72.3%,游离LDM组为70.9%,相比较长连接键的硫醚键偶联物抑瘤作用显著增强。Fab'-SSMPB-LDM和Fab'-SMBS-LDM组动物的平均生存时间延长为165.8%和145.2%,Fab'-SPDP-LDM和Fab'-LCSPDP-LDM组分别为82.2%和107.5%,LDM组为71.9%。与二硫键偶联物组比较...
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| 关 键 词： | 力达霉素 Ⅳ型胶原酶 靶向治疗 小型化 偶联剂 |
Comparison of the antitumor activities of immunoconjugates composed of lidamycin and monoclonal antibody fab' fragment with different linkers |
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| Feng Yun,Shao Rong-Guang,Dai Yao,Li Bao-Wei,He Hong-Wei,Ren Kai-Huan. Comparison of the antitumor activities of immunoconjugates composed of lidamycin and monoclonal antibody fab' fragment with different linkers[J]. Acta pharmaceutica Sinica, 2010, 45(5): 571-575 |
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| Authors: | Feng Yun Shao Rong-Guang Dai Yao Li Bao-Wei He Hong-Wei Ren Kai-Huan |
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| Affiliation: | FENG Yun1,SHAO Rong-guang2,DAI Yao2,LI Bao-wei2,HE Hong-wei2,REN Kai-huan2 (1.School of Medical Science , Laboratory Medicine of Jiangsu University,Zhenjiang 212013,China,2.Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing 100050,China) |
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| Abstract: | To investigate the antitumor activities of the immunoconjugates composed of anti-type IV collagenase monoclonal antibody Fab' fragment and lidamycin (LDM) prepared with different linkers.The immunoconjugates were prepared by linking Fab' to lysine-69 of LDM apoprotein by SPDP,LCSPDP,SMBS or SSMPB as the intermediate drug linkers.Immunoreactivities of the conjugates were determined by ELISA.The cytotoxicities of the conjugates were examined by clonogenic assay.In vivo antitumor effects of the conjugates were... |
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| Keywords: | lidamycin type IV collagenase target therapy miniaturization linker |
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