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Vaccine Detail
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STn-MUC1-TTox vaccine |
| Vaccine Information |
- Vaccine Name: STn-MUC1-TTox vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 VNTR, 20aa (PAHGVTSAPDTRPAPGSTAP), STn on T6(Kaiser et al., 2009); MUC1 VNTR, 22aa (PAHGVTSAPDTRPAPGSTAPPA), STn on S17(Stergiou et al., 2019)
- Immunization Route: Intraperitoneal injection (i.p.)
- Description: A fully synthetic conjugate vaccine consisting of a tumor-associated sialyl-Tn (STn) MUC1 tandem-repeat glycopeptide (20-mer (Kaiser et al., 2009)/22-mer (Stergiou et al., 2019) variants of PAHGVTSAPDTRPAPGSTAP) conjugated to Tetanus Toxoid (TTox) via triethylene glycol spacer and diethyl squarate chemistry, yielding ~40 glycopeptide molecules per TTox molecule (Kaiser et al., 2009). The glycopeptide incorporates STn (Neu5Acα2-6GalNAc) O-linked to threonine (Kaiser et al., 2009) or serine-17 of the GSTA motif (Stergiou et al., 2019), with two immunodominant regions (PDTR and GSTA)(Stergiou et al., 2019). Immunization of Balb/c mice (20 µg, CFA/IFA) induced strong IgG in all 10 mice (titers 1/100,000–1/200,000), with complete neutralization by homologous STn-MUC1, substantial inhibition by related MUC1 glycopeptides (Tn, sialyl-Tn/Tn, 2,6-sialyl-T variants), and minimal recognition of non-glycosylated MUC1, T-antigen glycopeptide, or MUC4 sequences (Kaiser et al., 2009). Preventive vaccination of WT mice (3×10 µg, IFA, i.p.) induced strong IgG1 and moderate IgG2b titers, significantly inhibiting tumor progression after PyMTxhuMUC1 transplantation (p≤0.01); in spontaneous tumor-bearing PyMTxhuMUC1-tg mice, vaccination reduced tumor size (p≤0.0001) and extended survival ~30 days (p≤0.001) with no autoimmune reactions, with IgG1 and IgG2a responses detected alongside elevated IgM; PyMT-tg mice lacking hu(TA)MUC1 showed no reduction, confirming antigen specificity; elevated IgM suggested residual T-cell tolerance (Stergiou et al., 2019). IHC of 35 TNBC specimens confirmed 97% hu(TA)MUC1 positivity with 74% high expressors (IRS 6–12) (Stergiou et al., 2019).
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| Host Response |
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| References |
Kaiser et al., 2009: Kaiser A, Gaidzik N, Westerlind U, Kowalczyk D, Hobel A, Schmitt E, Kunz H. A synthetic vaccine consisting of a tumor-associated sialyl-T(N)-MUC1 tandem-repeat glycopeptide and tetanus toxoid: induction of a strong and highly selective immune response. Angewandte Chemie (International ed. in English). 2009; 48(41); 7551-7555. [PubMed: 19685547].
Stergiou et al., 2019: Stergiou N, Gaidzik N, Heimes AS, Dietzen S, Besenius P, Jäkel J, Brenner W, Schmidt M, Kunz H, Schmitt E. Reduced Breast Tumor Growth after Immunization with a Tumor-Restricted MUC1 Glycopeptide Conjugated to Tetanus Toxoid. Cancer immunology research. 2019; 7(1); 113-122. [PubMed: 30413430].
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