Anti-Tumor Effects Of Different Lidamycin-Anti-Type Vi Collagenase Monoclonal Antibody Conjugates
Keywords
Abstract
Study the selective anti-tumor effect of lidamycin (ldm) and anti-type IV collagenase monoclonal antibody 3g11 immunoconjugates prepared by different coupling methods. Using spdp and smbs as coupling agents, the lysine at position 69 of the LDM prosthetic protein was connected to the 2-iminotetrahydrothiophene-modified monoclonal antibody 3g11 to prepare an immunoconjugate; the immune activity of the conjugate was measured by ELISA. The anti-tumor effects of the two conjugates were observed by cloning formation method and human ht-1080 cell immunodeficiency mouse transplantation model. The conjugate retained the immune activity of monoclonal antibody 3g11 against type IV collagenase, and the killing effect of 3g11-smbs-ldm on HT-1080 cells cultured in vitro was stronger than that of ldm and 3g11-spdp-ldm. Animal experiments show that the tumor inhibition rate of ldm under equimolar dosage conditions is 86.1%, the free ldm group is 71.2%, the 3g11-spdp-ldm group is 77.1%, the inhibitory effect of 3g11-smbs-ldm Significantly enhanced. The average survival time of animals in the 3g11-smbs-ldm group was extended to 163.7%, that of the 3g11-spdp-ldm group was 125.3%, and that of the ldm group was 71.9%. 3g11-smbs-ldm can significantly extend the survival time of tumor-bearing mice. There are significant differences between the two species. The 3g11-smbs-ldm conjugate has more selective anti-tumor effects, significantly improved efficacy, prolonged survival of tumor-bearing animals, and significantly reduced toxicity, and may become a new tumor treatment drug.
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Original research was done by Feng Yun, Zhen Yongsu, Dai Yao, Shang Boyang, Zhang Min, He Hongwei, Li Baobo, Shao Rongguang
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