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Vaccine Detail
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Linear Trivalent MUC1 PDT(Tn)RPAP-BSA Conjugate Vaccine |
| Vaccine Information |
- Vaccine Name: Linear Trivalent MUC1 PDT(Tn)RPAP-BSA Conjugate Vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: 21-mer MUC1 (PDTRPAP×3), Tn at T3, T10, T17 (Li et al., 2018)
- Immunization Route: subcutaneous injection
- Description: A synthetic conjugate vaccine composed of linear trivalent (trimeric) glycopeptide fragments of the MUC1 VNTR immunodominant motif PDTRPAP conjugated to bovine serum albumin (BSA) via squaric acid chemistry. Two candidates were prepared: non-glycosylated (candidate 10, R=H) and Tn-glycosylated (candidate 11, R=Tn). The Tn antigen building block was synthesized at scale via imidazole-1-sulfonyl azide-based azidation of D-galactosamine followed by Schmidt glycosylation and Fmoc-based solid-phase peptide synthesis (SPPS) on 2-chlorotrityl resin. The trivalent display was designed to exploit multivalent B-cell receptor engagement, while the non-natural glycopeptide structure and Tn glycosylation were intended to break immune self-tolerance and enhance immunogenicity relative to natural MUC1 glycopeptides. Both candidates were administered subcutaneously in female BALB/c mice (n=3 per group) at 10 µg per dose, four doses administered biweekly, with CFA/IFA adjuvant, eliciting high IgG antibody titers across all isotypes (IgG1, IgG2a, IgG2b, IgG3, IgM, IgA) with predominant IgG1, indicative of a Th2-biased humoral immune response. Non-glycosylated candidate 10 achieved higher overall antibody titers, while glycosylated candidate 11 demonstrated superior binding strength and specificity to MUC1-expressing MCF-7 human breast cancer cells by both FACS analysis and immunofluorescence confocal microscopy, despite its lower titers. The Tn glycosylation renders the epitope more 'foreign-like' compared to the 'self-like' unglycosylated MUC1, making candidate 11 more effective at breaking immune self-tolerance and achieving specific cancer cell recognition(Li et al., 2018).
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| References |
Li et al., 2018: Li M, Yu F, Yao C, Wang PG, Liu Y, Zhao W. Synthetic and immunological studies on trimeric MUC1 immunodominant motif antigen-based anti-cancer vaccine candidates. Organic & biomolecular chemistry. 2018; 16(6); 993-999. [PubMed: 29345713].
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