2. Academic Validation
  3. Therapeutic effect of a MUC1-specific monoclonal antibody-drug conjugates against pancreatic cancer model

Therapeutic effect of a MUC1-specific monoclonal antibody-drug conjugates against pancreatic cancer model

  • Cancer Cell Int. 2022 Dec 27;22(1):417. doi: 10.1186/s12935-022-02839-w.
Guang Wu # 1,  Lan Li # 2,  Mengnan Liu # 3,  Chunyan Chen 3,  Guangze Wang 3,  Zewei Jiang 3,  Yaqian Qin 4,  Licai He 3,  Hongzhi Li 3,  Jiawei Cao 3,  Haihua Gu 5
Affiliations

Affiliations

  • 1 Wenzhou Key Laboratory of Cancer Pathogenesis and Translation, Key Laboratory of Laboratory Medicine, School of Laboratory Medicine and Life Sciences, Ministry of Education, Wenzhou Medical University, Wenzhou, 325035, China. guangwu@wmu.edu.cn.
  • 2 School of Public Health and Management, Wenzhou Medical University, 325035, Wenzhou, China.
  • 3 Wenzhou Key Laboratory of Cancer Pathogenesis and Translation, Key Laboratory of Laboratory Medicine, School of Laboratory Medicine and Life Sciences, Ministry of Education, Wenzhou Medical University, Wenzhou, 325035, China.
  • 4 Medical Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
  • 5 Wenzhou Key Laboratory of Cancer Pathogenesis and Translation, Key Laboratory of Laboratory Medicine, School of Laboratory Medicine and Life Sciences, Ministry of Education, Wenzhou Medical University, Wenzhou, 325035, China. haihuagu@wmu.edu.cn.
  • # Contributed equally.
PMID: 36572921 DOI: 10.1186/s12935-022-02839-w
Abstract

Background: Pancreatic Cancer is one of the most aggressive malignancies without effective targeted therapies. MUC1 has emerged as a potential common target for Cancer therapy because it is overexpressed in a variety of different cancers including the majority of pancreatic Cancer. However, there are still no approved monoclonal antibody drugs targeting MUC1 have been reported. Recently, we generated a humanized MUC1 antibody (HzMUC1) specific to the interaction region between MUC1-N and MUC1-C. In this study, we generated the antibody drug conjugate (ADC) by conjugating HzMUC1 with monomethyl Auristatin (MMAE), and examined the efficacy of HzMUC1-MMAE against the MUC1-positive pancreatic Cancer in vitro and in vivo.

Methods: Western blot and immunoprecipitation were used to detect MUC1 in pancreatic Cancer cells. MUC1 localization in pancreatic Cancer cells was determined by confocal microscopy. HzMUC1 was conjugated with the monomethyl Auristatin (MMAE), generating the HzMUC1-MMAE ADC. Colony formation assay and flow cytometry were used to assess the effects of the HzMUC1-MMAE cell viability, cell cycle progression and Apoptosis. Capan-2 and CFPAC-1 xenograft model were used to test the efficacy of HzMUC1-MMAE against pancreatic Cancer.

Results: HzMUC1 antibody binds to MUC1 on the cell surface of pancreatic Cancer cells. HzMUC1-MMAE significantly inhibited cell growth by inducing G2/M cell cycle arrest and Apoptosis in pancreatic Cancer cells. Importantly, HzMUC1-MMAE significantly reduced the growth of pancreatic xenograft tumors by inhibiting cell proliferation and enhancing cell death.

Conclusion: Our results indicate that HzMUC1-ADC is a promising novel targeted therapy for pancreatic Cancer. HzMUC1-ADC should also be an effective drug for the treatment of different MUC1-positive cancers.

Keywords

Antibody-drug conjugate; Humanized monoclonal antibody; MMAE; Mucin1; Pancreatic cancer.

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