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Vaccine Detail
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MUC1 60-mer Tn/STn Glycopeptide-KLH Conjugate Vaccine |
| Vaccine Information |
- Vaccine Name: MUC1 60-mer Tn/STn Glycopeptide-KLH Conjugate Vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 (Sørensen et al., 2006)
- Immunization Route: subcutaneous injection
- Description: A glycopeptide conjugate vaccine containing chemoenzymatically synthesized MUC1 60-mer tandem repeat sequences with complete Tn or STn O-glycosylation at all five sites per repeat (15 total) conjugated to keyhole limpet hemocyanin (KLH). Glycopeptides are synthesized using site-selective recombinant human GalNAc-transferases (GalNAc-T2, -T4, -T11) and ST6GalNAc-I to achieve complete O-glycan occupancy with Tn (GalNAcα1-O-Ser/Thr) or STn (NeuAcα2-6GalNAcα1-O-Ser/Thr) structures. Complete O-glycan occupancy elicited the strongest antibody responses in both wild-type Balb/c and MUC1 transgenic mice, with predominantly IgG1 and IgG2A/IgG2B class switching, overcoming immune tolerance where previous MUC1 peptide vaccines had failed. Induced antibodies showed cancer-specific reactivity with increased Tn/STn recognition and decreased reactivity with unglycosylated MUC1 and T/ST glycoforms, demonstrating minimal anti-hapten responses. Monoclonal antibody 5E5 generated from immunized mice stained 18/18 ductal carcinomas, 1/2 lobular carcinomas, and only 2/6 benign lesions (<25% cells), showing higher cancer specificity than control antibody HMFG2. Immune responses required combined glycopeptide epitopes with both peptide sequence and carbohydrate structures. MUC1 is a membrane-bound mucin glycoprotein overexpressed with simplified O-glycans (Tn/STn) in adenocarcinomas including breast, ovarian, and pancreatic cancers (Sørensen et al., 2006).
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| Host Response |
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| References |
Sørensen et al., 2006: Sørensen AL, Reis CA, Tarp MA, Mandel U, Ramachandran K, Sankaranarayanan V, Schwientek T, Graham R, Taylor-Papadimitriou J, Hollingsworth MA, Burchell J, Clausen H. Chemoenzymatically synthesized multimeric Tn/STn MUC1 glycopeptides elicit cancer-specific anti-MUC1 antibody responses and override tolerance. Glycobiology. 2006; 16(2); 96-9107. [PubMed: 16207894].
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