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Vaccine Detail
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sp²-Iminosugar Tn Mimic MUC1 Glycopeptide-KLH Conjugate Vaccine |
| Vaccine Information |
- Vaccine Name: sp²-Iminosugar Tn Mimic MUC1 Glycopeptide-KLH Conjugate Vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 (Bermejo et al., 2020)
- Immunization Route: Intradermal injection (i.d.)
- Description: A synthetic glycopeptide-protein conjugate cancer vaccine containing a MUC1 epitope glycosylated with an unnatural sp²-iminosugar-based Tn antigen mimic, conjugated to keyhole limpet hemocyanin (KLH) carrier protein. The sp²-iminosugar modification replaces the natural O-glycosidic bond with a chemically and enzymatically stable sp²-hybridized pseudoamide linkage. Vaccination with sp²-iminosugar Tn mimic MUC1 glycopeptide-KLH conjugate vaccine elicits higher levels of specific anti-MUC1 IgG antibodies compared to the natural Tn antigen vaccine (P < 0.05), with predominantly IgG1 subtype (IgG1 > IgG2a). The elicited antibodies selectively recognize human breast cancer cells (MCF7, T47D) expressing tumor-associated MUC1, but not HEK293T cells lacking tumor-associated MUC1. A related glycopeptide containing the sp²-iminosugar Tn mimic exhibits 2-fold higher binding affinity to anti-MUC1 antibody scFv-SM3 (K_D = 1.60 ± 0.16 μM) compared to the natural Tn variant (K_D = 3.30 ± 0.84 μM). In this vaccine, the MUC1 glycopeptide is conjugated to KLH, an immunostimulant and hapten carrier, to enhance immune recognition. MUC1 antigen, a membrane-bound glycoprotein expressed by most glandular and ductal epithelial cells, is overexpressed in an aberrant or deglycosylated form in various cancers such as those of the breast, prostate, and ovary (Bermejo et al., 2020).
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| Host Response |
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| References |
Bermejo et al., 2020: Bermejo IA, Navo CD, Castro-López J, Guerreiro A, Jiménez-Moreno E, Sánchez Fernández EM, García-Martín F, Hinou H, Nishimura SI, García Fernández JM, Mellet CO, Avenoza A, Busto JH, Bernardes GJL, Hurtado-Guerrero R, Peregrina JM, Corzana F. Synthesis, conformational analysis and in vivo assays of an anti-cancer vaccine that features an unnatural antigen based on an sp(2)-iminosugar fragment. Chemical science. 2020; 11(15); 3996-4006. [PubMed: 34122869].
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