【摘 要】
：
Mucin 1 (MUC1) has been regarded as an ideal target for cancer treatment,since it is overexpressed in a variety of different cancers including the majority of breast cancer.However,there are still no approved monoclonal antibody drugs targeting MUC1.In th
【机 构】
：
Key Laboratory of Laboratory Medicine,Ministry of Education,School of Laboratory Medicine and Life S
论文部分内容阅读
Mucin 1 (MUC1) has been regarded as an ideal target for cancer treatment,since it is overexpressed in a variety of different cancers including the majority of breast cancer.However,there are still no approved monoclonal antibody drugs targeting MUC1.In this study,we generated a human-ized MUC1 (HzMUC1) antibody from our previously developed MUC1 mouse monoclonal antibody that only recognizes MUC1 on the surface of tumor cells.Furthermore,an antibody-drug conju-gate (ADC) was generated by conjugating HzMUC1 with monomethyl auristatin (MMAE),and the efficacy of HzMUC1-MMAE on the MUC1-positive HER2+ breast cancer in vitro and in \'Xenograft\'model was tested.Results from western blot analysis and immunoprecipitation revealed that the HzMUC1 antibody did not recognize cell-free MUC1-N in sera from breast cancer patients.Confocal microscopy analysis showed that HzMUC1 antibody bound to MUC1 on the surface of breast can-cer cells.Results from mapping experiments suggested that HzMUC1 may recognize an epitope present in the interaction region between MUC1-N and MUC1-C.Results from colony formation assay and flow cytometry demonstrated that HzMUC1-MMAE significantly inhibited cell growth by inducing G2/M cell cycle arrest and apoptosis in trastuzumab-resistant HER2-positive breast cancer cells.Meanwhile,HzMUC1-MMAE significantly reduced the growth of HCC1954 xenograft tumors by inhibiting cell proliferation and enhancing cell death.In conclusion,our results indicate that HzMUC1-ADC is a novel therapeutic drug that can overcome trastuzumab resistance of breast cancer.HzMUC1-ADC should also be an effective therapeutic drug for the treatment of different MUC1-positive cancers in clinic.
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