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Vaccine Detail
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Sialyl-Tn-MUC1(22)-TTox conjugate vaccine (T6-APDTRP or S17/T18-GSTA variants) |
| Vaccine Information |
- Vaccine Name: Sialyl-Tn-MUC1(22)-TTox conjugate vaccine (T6-APDTRP or S17/T18-GSTA variants)
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: 22-mer MUC1 glycopeptide (PAHGVTSAPDTRPAPGSTAPPA; T6-APDTRP and S17/T18-GSTA variants) (Gaidzik et al., 2011)
- Immunization Route: subcutaneous injection
- Description: A fully synthetic conjugate vaccine composed of sialyl-Tn–modified MUC1 22-mer glycopeptide antigens coupled to tetanus toxoid (TTox) as carrier protein via squaric acid diethyl ester linker chemistry. Vaccine 13 carries the sialyl-Tn antigen at threonine-6, while vaccine 14 carries the sialyl-Tn antigen at serine-17/threonine-18 of the GSTA region of the MUC1 tandem repeat sequence. The 22-mer peptide incorporates both the APDTRP immunodominant motif and the GSTA conformational epitope, the latter recognized by tumor-selective antibody SM3 and autoantibodies in cancer patient sera. Approximately 20 glycopeptide molecules are loaded per TTox molecule. Immunization of Balb/cJ mice induced IgG1 antibody titers of ~1/30,000 in all vaccinated mice, breaking natural self-tolerance. Both vaccines induced strong MCF-7 breast tumor cell binding. Vaccine 13 (Thr-6) recognition profile differed from SM3 and patient autoantibodies. Vaccine 14 (Ser-17/Thr-18) showed superior selectivity versus SM3, additionally induced strong T-47D breast tumor cell binding, and binding was fully neutralized by sialyl-Tn MUC1 glycopeptide 8, confirming structure selectivity; immunohistochemical staining of native patient breast tumor tissue sections showed grade-dependent binding (G1 <1% → G2 1–9% → G3 10–50% reacting cells) with no normal tissue staining. MUC1 is a membrane-bound glycoprotein overexpressed in an aberrantly glycosylated form in epithelial cancers including breast, pancreatic, and ovarian cancers, bearing truncated, prematurely sialylated glycans (Tn, sialyl-Tn, T, sialyl-T antigens) that expose peptide epitopes otherwise masked in normal tissue (Gaidzik et al., 2011).
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| Host Response |
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| References |
Gaidzik et al., 2011: Gaidzik N, Kaiser A, Kowalczyk D, Westerlind U, Gerlitzki B, Sinn HP, Schmitt E, Kunz H. Synthetic antitumor vaccines containing MUC1 glycopeptides with two immunodominant domains-induction of a strong immune response against breast tumor tissues. Angewandte Chemie (International ed. in English). 2011; 50(42); 9977-9981. [PubMed: 21910197].
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