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Vaccine Detail
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MUC1(Tn)/MUC1(STn)/MUC1(2,3-ST)–TT Mosaic Glycopeptide Vaccine |
| Vaccine Information |
- Vaccine Name: MUC1(Tn)/MUC1(STn)/MUC1(2,3-ST)–TT Mosaic Glycopeptide Vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: 3× MUC1 VNTR (HGVTSAPDTRPAPGSTAPPA), Tn/STn/2,3-ST at T9 (Wu et al., 2026)
- Immunization Route: subcutaneous injection
- Description: A mosaic glycopeptide conjugate vaccine composed of three aberrantly glycosylated MUC1 glycopeptides — MUC1(Tn), MUC1(STn), and MUC1(2,3-ST) — simultaneously conjugated to tetanus toxoid (TT) via a squaric acid linker, formulated with alum adjuvant. Each glycopeptide is based on the full-length 20 aa MUC1 VNTR sequence (HGVTSAPDTRPAPGSTAPPA) with glycosylation at Thr9, synthesized by solid-phase peptide synthesis and chemoenzymatic extension. The mosaic design presents multiple tumor-associated glycoforms on a single carrier protein to address MUC1 glycan heterogeneity on tumor cell surfaces. Immunization of both wild-type C57BL/6 and human MUC1 transgenic (MUC1.Tg) mice elicited higher IgG1-dominant antibody titers than single-glycoform or cocktail formulations, with broad-spectrum recognition of 6 MUC1 glycoforms (Tn, STn, T, 2,3-ST, 2,6-ST, DST). Vaccine-induced antibodies demonstrated enhanced binding to MUC1-expressing tumor cells (B16-MUC1, PANC-1) and mediated ~70% tumor cell lysis via ADCC, with no CDC activity. In vivo, the vaccine achieved 83.9% tumor growth inhibition in MUC1.Tg mice and 1.65–2.17-fold extended median survival in WT mice (12.5% alive at day 90), outperforming both single-glycoform and cocktail vaccines. Mechanistic studies revealed enhanced DC and B cell activation, increased IFN-γ production in CD4⁺/CD8⁺ T cells, elevated CD8⁺/CD4⁺ effector memory T cells, increased CD8⁺ tumor infiltration, and decreased intratumoral Treg cells. CTL assays demonstrated reduced target cell viability to 39.3% in WT and 78.8% in MUC1.Tg mice. Combination with anti-PD-1 checkpoint blockade further extended survival beyond vaccine monotherapy. In therapeutic settings, the vaccine achieved 67% tumor growth inhibition and 1.4-fold extended median survival. Vaccine-induced antibodies selectively bound patient-derived pancreatic tumor tissues with minimal peritumoral normal tissue reactivity, supporting clinical translational potential (Wu et al., 2026).
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| Host Response |
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| References |
Wu et al., 2026: Wu Y, Ma W, Jiang Y, Ling Y, Zhou Y, Guo Y, Hong S, Ding F, Zhang J, Li B, Liang H, Wang Z, Li Y, Li T, Cai H. A Glycopeptide Mosaic Vaccine Elicits Robust Antitumor Immunity by Targeting Glycan Heterogeneity. JACS Au. 2026; 6(1); 469-482. [PubMed: 41614196].
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