Antitumor effects of the molecule-downsized immunoconjugate composed of lidamycin and Fab′fragment of monoclonal antibody directed against type IV collagenase |
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作者姓名: | WANG Fengqiang SHANG Boyang & ZHEN YongsuInstitute of Medicinal Biotechnology Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100050 China |
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作者单位: | WANG Fengqiang,SHANG Boyang & ZHEN YongsuInstitute of Medicinal Biotechnology,Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing 100050,China |
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摘 要: | Type IV collagenase plays an important role in tumor invasion and metastasis through cleaving type IV collagen in the basement membrane and extracellular matrix. In this study a molecule-downsized immunoconjugate (Fab'-LDM) was constructed by linking lidamycin (LDM), a highly potent antitumor antibiotic, to the Fab' fragment of a monoclonal antibody directed against type IV collagenase and its antitumor effect was investigated. As assayed in 10% SDS-PAGE gel, the molecular weight of Fab'-LDM conjugate was 65 kD with a 1 : 1 molecular ratio of Fab' and LDM. The Fab'-LDM conjugate maintained most part of the immunoreactivity of Fab' fragment to both type IV collagense and mouse hepatoma 22 cells by ELISA. By MTT assay, Fab'-LDM conjugate showed more potent cytotoxicity to hepatoma 22 cells than that of LDM. Administered intravenously, Fab'-LDM conjugate proved to be more effective against the growth of subcutaneously transplanted hepatoma 22 in mice than free LDM in two experiment settings. In Experiment
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收稿时间: | 2003-04-07 |
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