Anti-Tumor Effect Of Miniaturized Monoclonal Antibody Immunoconjugates Targeting Type Iv Collagenase
Keywords
Monoclonal Antibody Immunoconjugate, Lidamycin, Antibody Drug, Anti-Type Iv Collagenase Monoclonal Antibody
Abstract
Type IV collagenase is closely related to tumor invasion, metastasis, and neovascularization. Using type IV collagenase as a molecular target, a mouse anti-type IV collagenase monoclonal antibody was used to construct a miniaturized Fab’ fragment and a high-efficiency anti- Immunoconjugate (Fab’-LDM) of the tumor antibiotic lidamycin (LDM). The molecular weight of the conjugate is about 65kD, and the coupling molecule ratio is 1:1. Detected by ELISA method, Fab’-LDM conjugate The conjugate retained the immunobinding activity of the monoclonal antibody Fab’ fragment against liver cancer 22 (H22) cells; measured by the MTT method, the Fab’-LDM conjugate showed stronger cytotoxicity against liver cancer 22 cells. In vivo animal experiments observed that it has The efficacy of transplanted liver cancer 22 in mice, mice were inoculated with tumors subcutaneously, and administration started 24 hours later (intravenous injection twice, 1 and 8 days after inoculation), Fab’-LDM conjugate 0.025, 0.05 and 0.10 mg/kg The tumor inhibition rates of the dose groups were 76.7%, 93.3% and 94.8% respectively, while the tumor inhibition rate of free LDM 0.05 mg/kg was 76.1%; another batch of experiments started administration 96 hours after tumor inoculation (intravenous injection twice, 4 and 11 days after vaccination respectively), the tumor inhibition rates of the Fab’-LDM conjugate 0.025 and 0.05 mg/kg groups were 74.2% and 80.9%, respectively, while the tumor inhibition rate of the LDM 0.05 mg/kg group was 60.5%. .Fab’-LDM conjugate 0.05mg/kg can significantly prolong the survival time of tumor-bearing mice. Compared with the same dose of free LDM, the effect of prolonging survival time is stronger (P<0.05). The above results show that with Miniaturized monoclonal antibody immunoconjugates targeting type IV collagenase have significant efficacy in the experimental treatment of tumors. For further information of this article and research, feel free to contact our team for asssitance. Original research was done by Wang Fengqiang, Shang Boyang, Zhen Yongsu
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