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Vaccine Detail
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MUC1-STn/Tn glycopeptide-poliovirus T-helper epitope-Pam3CysSK4 vaccine |
| Vaccine Information |
- Vaccine Name: MUC1-STn/Tn glycopeptide-poliovirus T-helper epitope-Pam3CysSK4 vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: 11-mer MUC1 (GTSAPDTRPAP), STn/Tn at T2 (Thompson et al., 2015)
- Immunization Route: Intradermal injection (i.d.)
- Description: A fully synthetic three-component glycolipopeptide cancer vaccine candidate composed of a MUC1-derived glycopeptide bearing the sialyl-Tn (STn; αNeu5Ac-(2,6)-αGalNAc-Thr) tumor-associated carbohydrate antigen as the B-cell epitope, a promiscuous helper T-cell epitope derived from the poliovirus, and the TLR2 agonist Pam3CysSK4, all covalently linked without artificial linkers via microwave-assisted solid-phase peptide synthesis (MW-SPPS) and formulated in liposomes. In MUC1 transgenic mice (C57BL/6; H-2b) immunized intradermally five times at biweekly intervals, the STn-containing vaccine (compound 1) elicited total IgG titers of 12,700 and the Tn-containing analog (compound 2) elicited 29,200, both with mixed Th1/Th2 profiles (compound 1 IgG subclasses — IgG1: 3,700; IgG2a: 900; IgG2b: 2,800; IgG3: 5,100). Both compounds 1 and 2 induced significant ADCC-mediated lysis of MUC1-expressing C57mg mammary cancer cells (P<0.001 vs control). Strong CD4+IFNγ+ and CD8+IFNγ+ T-cell responses were activated, with the STn-containing vaccine eliciting somewhat stronger CTL responses compared to the Tn-containing analog by ELISPOT. Critically, vaccine-primed CD62Llow T-cells were restimulated by B16.MUC1 tumor cells (P<0.001), demonstrating breaking of immune tolerance in MUC1.Tg mice. This fully synthetic approach, devoid of immunosuppressive carrier proteins, demonstrated superior immunogenicity compared to the STn-KLH conjugate that previously failed in Phase III clinical trials (Thompson et al., 2015).
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| Host Response |
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| References |
Thompson et al., 2015: Thompson P, Lakshminarayanan V, Supekar NT, Bradley JM, Cohen PA, Wolfert MA, Gendler SJ, Boons GJ. Linear synthesis and immunological properties of a fully synthetic vaccine candidate containing a sialylated MUC1 glycopeptide. Chemical communications (Cambridge, England). 2015; 51(50); 10214-10217. [PubMed: 26022217].
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