MUC1 Therapeutic Tumor Vaccine in Advanced Solid Cancers

Summary

This is an investigator-initiated, single-center, open, single-arm, exploratory study of a therapeutic cancer vaccine for the treatment of advanced solid tumors. A dose-escalation trial is being conducted in subjects diagnosed with advanced solid tumors to evaluate the safety and tolerability of the cancer vaccine in subjects with advanced solid tumors and to preliminarily evaluate the efficacy of the tumor vaccine in subjects with advanced solid tumors.

Timeline

Start

2023-08

Primary completion

2023-12

Completion

2024-12

Publications

• Background Arnold M, Morgan E, Rumgay H, Mafra A, Singh D, Laversanne M, Vignat J, Gralow JR, Cardoso F, Siesling S, Soerjomataram I. Current and future burden of breast cancer: Global statistics for 2020 and 2040. Breast. 2022 Dec;66:15-23. doi: 10.1016/j.breast.2022.08.010. Epub 2022 Sep 2.
• Background Rumgay H, Shield K, Charvat H, Ferrari P, Sornpaisarn B, Obot I, Islami F, Lemmens VEPP, Rehm J, Soerjomataram I. Global burden of cancer in 2020 attributable to alcohol consumption: a population-based study. Lancet Oncol. 2021 Aug;22(8):1071-1080. doi: 10.1016/S1470-2045(21)00279-5.
• Background O'Donnell JS, Teng MWL, Smyth MJ. Cancer immunoediting and resistance to T cell-based immunotherapy. Nat Rev Clin Oncol. 2019 Mar;16(3):151-167. doi: 10.1038/s41571-018-0142-8.
• Background Lei K, Kurum A, Kaynak M, Bonati L, Han Y, Cencen V, Gao M, Xie YQ, Guo Y, Hannebelle MTM, Wu Y, Zhou G, Guo M, Fantner GE, Sakar MS, Tang L. Cancer-cell stiffening via cholesterol depletion enhances adoptive T-cell immunotherapy. Nat Biomed Eng. 2021 Dec;5(12):1411-1425. doi: 10.1038/s41551-021-00826-6. Epub 2021 Dec 6.
• Background Riley RS, June CH, Langer R, Mitchell MJ. Delivery technologies for cancer immunotherapy. Nat Rev Drug Discov. 2019 Mar;18(3):175-196. doi: 10.1038/s41573-018-0006-z.
• Background Szeto GL, Finley SD. Integrative Approaches to Cancer Immunotherapy. Trends Cancer. 2019 Jul;5(7):400-410. doi: 10.1016/j.trecan.2019.05.010.
• Background Zhang Y, Zhang Z. The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications. Cell Mol Immunol. 2020 Aug;17(8):807-821. doi: 10.1038/s41423-020-0488-6. Epub 2020 Jul 1.
• Background Gao T, Cen Q, Lei H. A review on development of MUC1-based cancer vaccine. Biomed Pharmacother. 2020 Dec;132:110888. doi: 10.1016/j.biopha.2020.110888. Epub 2020 Oct 21.
• Background Nabavinia MS, Gholoobi A, Charbgoo F, Nabavinia M, Ramezani M, Abnous K. Anti-MUC1 aptamer: A potential opportunity for cancer treatment. Med Res Rev. 2017 Nov;37(6):1518-1539. doi: 10.1002/med.21462. Epub 2017 Jul 31.
• Background Hossain MK, Wall KA. Immunological Evaluation of Recent MUC1 Glycopeptide Cancer Vaccines. Vaccines (Basel). 2016 Jul 26;4(3):25. doi: 10.3390/vaccines4030025.
• Background Park JA, Park S, Park HB, Han MK, Lee Y. MUC1-C Contributes to the Maintenance of Human Embryonic Stem Cells and Promotes Somatic Cell Reprogramming. Stem Cells Dev. 2021 Nov 1;30(21):1082-1091. doi: 10.1089/scd.2021.0185. Epub 2021 Oct 18.
• Background Rajabi H, Kufe D. MUC1-C Oncoprotein Integrates a Program of EMT, Epigenetic Reprogramming and Immune Evasion in Human Carcinomas. Biochim Biophys Acta Rev Cancer. 2017 Aug;1868(1):117-122. doi: 10.1016/j.bbcan.2017.03.003. Epub 2017 Mar 14.
• Background Nath S, Mukherjee P. MUC1: a multifaceted oncoprotein with a key role in cancer progression. Trends Mol Med. 2014 Jun;20(6):332-42. doi: 10.1016/j.molmed.2014.02.007. Epub 2014 Mar 22.
• Background Chen W, Zhang Z, Zhang S, Zhu P, Ko JK, Yung KK. MUC1: Structure, Function, and Clinic Application in Epithelial Cancers. Int J Mol Sci. 2021 Jun 18;22(12):6567. doi: 10.3390/ijms22126567.
• Background Macao B, Johansson DG, Hansson GC, Hard T. Autoproteolysis coupled to protein folding in the SEA domain of the membrane-bound MUC1 mucin. Nat Struct Mol Biol. 2006 Jan;13(1):71-6. doi: 10.1038/nsmb1035. Epub 2005 Dec 20.
• Background Raina D, Kharbanda S, Kufe D. The MUC1 oncoprotein activates the anti-apoptotic phosphoinositide 3-kinase/Akt and Bcl-xL pathways in rat 3Y1 fibroblasts. J Biol Chem. 2004 May 14;279(20):20607-12. doi: 10.1074/jbc.M310538200. Epub 2004 Mar 3.
• Background Ota S, Miyashita M, Yamagishi Y, Ogasawara M. Baseline immunity predicts prognosis of pancreatic cancer patients treated with WT1 and/or MUC1 peptide-loaded dendritic cell vaccination and a standard chemotherapy. Hum Vaccin Immunother. 2021 Dec 2;17(12):5563-5572. doi: 10.1080/21645515.2021.2003645. Epub 2021 Dec 17.

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Indications