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Vaccine Detail
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MUC1-Tn-alpha-MeSer-Pam2Cys Liposomal Vaccine |
| Vaccine Information |
- Vaccine Name: MUC1-Tn-alpha-MeSer-Pam2Cys Liposomal Vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 (Martínez-Sáez et al., 2016)
- Immunization Route: subcutaneous injection
- Description: A synthetic tripartite cancer vaccine containing a MUC1 tumor-associated glycopeptide epitope conjugated with a TLR2 agonist adjuvant and incorporated into liposomes, with potential antineoplastic activity. The vaccine comprises: (1) a MUC1 PDTR epitope (APDTRPAP sequence) glycosylated with the Tn antigen (α-O-GalNAc) at an unnatural quaternary amino acid (α-methylserine) replacing threonine, (2) a PADRE universal T-helper epitope, and (3) Pam₂Cys as a covalently-linked TLR2 agonist adjuvant. All three components are covalently conjugated and formulated in phospholipid-based liposomes. Vaccination in MUC1.Tg mice elicited robust anti-MUC1 IgG antibody responses (median IgG total: 19,000; IgG1: 4,900; IgG2a: 1,900; IgG2b: 9,900; IgG3: 15,000) with mixed Th1/Th2 profile, significantly higher than empty liposome controls. Antibodies recognized both glycosylated and unglycosylated tumor-associated MUC1 epitopes with similar titers and demonstrated specific binding to MUC1-expressing MCF7 human breast cancer and C57mg.MUC1 mammary tumor cells. The unnatural glycopeptide exhibited approximately 1.8-fold enhanced stability in human serum compared to the natural threonine-containing analogue. However, immunogenicity was comparable to the natural threonine vaccine, with conformational studies revealing increased glycosidic linkage flexibility that may limit immune recognition despite improved proteolytic stability. MUC1 antigen, a membrane-bound glycoprotein expressed by most glandular and ductal epithelial cells, is overexpressed in aberrant or underglycosylated form in various cancers including breast, ovarian, and prostate cancers (Martínez-Sáez et al., 2016).
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| Host Response |
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| References |
Martínez-Sáez et al., 2016: Martínez-Sáez N, Supekar NT, Wolfert MA, Bermejo IA, Hurtado-Guerrero R, Asensio JL, Jiménez-Barbero J, Busto JH, Avenoza A, Boons GJ, Peregrina JM, Corzana F. Mucin architecture behind the immune response: design, evaluation and conformational analysis of an antitumor vaccine derived from an unnatural MUC1 fragment. Chemical science. 2016; 7(3); 2294-2301. [PubMed: 29910919].
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