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Vaccine Detail
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Pam3CysSK4–MUC1-Tn glycolipopeptide vaccine |
| Vaccine Information |
- Vaccine Name: Pam3CysSK4–MUC1-Tn glycolipopeptide vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 VNTR (22-mer, APGSTAPPAHGVTSAPDTRPAP), Tn at T18 (Supekar et al., 2018)
- Immunization Route: Intradermal injection (i.d.)
- Description: A fully synthetic multicomponent cancer vaccine composed of a long MUC1-derived glycopeptide (APGSTAPPAHGVTSAPDT(O-GalNAc)RPAP) covalently linked to the TLR2 lipopeptide self-adjuvant Pam2Cys, containing no artificial linkers or exogenous helper T-epitopes. The construct incorporates an endogenous promiscuous MHC class II helper T-epitope (STAPPAHGVTSA), MHC class I epitopes (STAPPAHGV, PAHGVTSA), and the established B-epitope SAPDT(O-GalNAc)RPAP, with a single GalNAc O-glycan on the threonine of the SAPDTRPAP epitope. Formulated as a liposomal preparation for intradermal immunization of MUC1.Tg mice (C57BL/6; H-2b) four times at biweekly intervals using the C57mg.MUC1 mammary cancer model. Vaccination elicited robust IgG antibody titers 10–77× higher than controls against both monoglycosylated (23,200 vs. 300–2,000 controls) and pentaglycosylated (21,700 vs. 0–1,200 controls) MUC1 epitopes. IgG subtyping revealed a mixed Th1/Th2 response (IgG1: 29,200; IgG2a: 1,200; IgG2b: 3,600; IgG3: 5,800) with very low IgM titers (300), demonstrating efficient class switching. Antisera showed specific binding to MUC1-expressing C57mg.MUC1 mammary cancer cells but not MUC1-negative wild-type C57mg cells. Significantly increased ADCC-mediated tumor cell lysis was observed compared to controls (p<0.05). ELISPOT analysis confirmed robust MUC1-specific IFNγ spot formation in CD62L^low T-cells without in vitro stimulation (p<0.05), and ICC staining confirmed activation of both CD4+IFNγ+ and CD8+IFNγ+ T-cells (p<0.05), demonstrating engagement of all three arms of the immune system(Supekar et al., 2018).
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| Host Response |
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| References |
Supekar et al., 2018: Supekar NT, Lakshminarayanan V, Capicciotti CJ, Sirohiwal A, Madsen CS, Wolfert MA, Cohen PA, Gendler SJ, Boons GJ. Synthesis and Immunological Evaluation of a Multicomponent Cancer Vaccine Candidate Containing a Long MUC1 Glycopeptide. Chembiochem : a European journal of chemical biology. 2018; 19(2); 121-125. [PubMed: 29120508].
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