Therapeutic effect of a MUC1-specific monoclonal antibody-drug conjugates against pancreatic cancer model
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,...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12935-022-02839-w |
| _version_ | 1797973470000185344 |
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| author | Guang Wu Lan Li Mengnan Liu Chunyan Chen Guangze Wang Zewei Jiang Yaqian Qin Licai He Hongzhi Li Jiawei Cao Haihua Gu |
| author_facet | Guang Wu Lan Li Mengnan Liu Chunyan Chen Guangze Wang Zewei Jiang Yaqian Qin Licai He Hongzhi Li Jiawei Cao Haihua Gu |
| author_sort | Guang Wu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T04:04:58Z |
| format | Article |
| id | doaj.art-38ecd02b445d47b4a434af9eaac2f9d3 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-04-11T04:04:58Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-38ecd02b445d47b4a434af9eaac2f9d32023-01-01T12:28:09ZengBMCCancer Cell International1475-28672022-12-0122111410.1186/s12935-022-02839-wTherapeutic effect of a MUC1-specific monoclonal antibody-drug conjugates against pancreatic cancer modelGuang Wu0Lan Li1Mengnan Liu2Chunyan Chen3Guangze Wang4Zewei Jiang5Yaqian Qin6Licai He7Hongzhi Li8Jiawei Cao9Haihua Gu10Wenzhou Key Laboratory of Cancer Pathogenesis and Translation, Key Laboratory of Laboratory Medicine, School of Laboratory Medicine and Life Sciences, Ministry of Education, Wenzhou Medical UniversitySchool of Public Health and Management, Wenzhou Medical UniversityWenzhou Key Laboratory of Cancer Pathogenesis and Translation, Key Laboratory of Laboratory Medicine, School of Laboratory Medicine and Life Sciences, Ministry of Education, Wenzhou Medical UniversityWenzhou Key Laboratory of Cancer Pathogenesis and Translation, Key Laboratory of Laboratory Medicine, School of Laboratory Medicine and Life Sciences, Ministry of Education, Wenzhou Medical UniversityWenzhou Key Laboratory of Cancer Pathogenesis and Translation, Key Laboratory of Laboratory Medicine, School of Laboratory Medicine and Life Sciences, Ministry of Education, Wenzhou Medical UniversityWenzhou Key Laboratory of Cancer Pathogenesis and Translation, Key Laboratory of Laboratory Medicine, School of Laboratory Medicine and Life Sciences, Ministry of Education, Wenzhou Medical UniversityMedical Research Center, The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou Key Laboratory of Cancer Pathogenesis and Translation, Key Laboratory of Laboratory Medicine, School of Laboratory Medicine and Life Sciences, Ministry of Education, Wenzhou Medical UniversityWenzhou Key Laboratory of Cancer Pathogenesis and Translation, Key Laboratory of Laboratory Medicine, School of Laboratory Medicine and Life Sciences, Ministry of Education, Wenzhou Medical UniversityWenzhou Key Laboratory of Cancer Pathogenesis and Translation, Key Laboratory of Laboratory Medicine, School of Laboratory Medicine and Life Sciences, Ministry of Education, Wenzhou Medical UniversityWenzhou Key Laboratory of Cancer Pathogenesis and Translation, Key Laboratory of Laboratory Medicine, School of Laboratory Medicine and Life Sciences, Ministry of Education, Wenzhou Medical UniversityAbstract 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.https://doi.org/10.1186/s12935-022-02839-wMucin1Humanized monoclonal antibodyAntibody-drug conjugateMMAEPancreatic cancer |
| spellingShingle | Guang Wu Lan Li Mengnan Liu Chunyan Chen Guangze Wang Zewei Jiang Yaqian Qin Licai He Hongzhi Li Jiawei Cao Haihua Gu Therapeutic effect of a MUC1-specific monoclonal antibody-drug conjugates against pancreatic cancer model Cancer Cell International Mucin1 Humanized monoclonal antibody Antibody-drug conjugate MMAE Pancreatic cancer |
| title | Therapeutic effect of a MUC1-specific monoclonal antibody-drug conjugates against pancreatic cancer model |
| title_full | Therapeutic effect of a MUC1-specific monoclonal antibody-drug conjugates against pancreatic cancer model |
| title_fullStr | Therapeutic effect of a MUC1-specific monoclonal antibody-drug conjugates against pancreatic cancer model |
| title_full_unstemmed | Therapeutic effect of a MUC1-specific monoclonal antibody-drug conjugates against pancreatic cancer model |
| title_short | Therapeutic effect of a MUC1-specific monoclonal antibody-drug conjugates against pancreatic cancer model |
| title_sort | therapeutic effect of a muc1 specific monoclonal antibody drug conjugates against pancreatic cancer model |
| topic | Mucin1 Humanized monoclonal antibody Antibody-drug conjugate MMAE Pancreatic cancer |
| url | https://doi.org/10.1186/s12935-022-02839-w |
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