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Vaccine Detail
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Q?-MUC1-Tf/STn Vaccine |
| Vaccine Information |
- Vaccine Name: Q?-MUC1-Tf/STn Vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 (Wu et al., 2019)
- Immunization Route: subcutaneous injection
- Description: Two MUC1 glycopeptide vaccine variants were developed using the 9-amino acid protective epitope SAPDTRPAP glycosylated at threonine with either Thomsen-Friedenreich (Tf: ?Gal-(1,3)-?GalNAc) or Sialyl Thomsen-nouveau (STn: ?Neu5Ac-(2,6)-?GalNAc) tumor-associated antigens, covalently conjugated to bacteriophage Q? virus-like particles (~270 glycopeptides per particle) and administered with MPLA adjuvant via subcutaneous route on days 0, 14, and 28. In MUC1 transgenic mice modeling immune tolerance, both constructs elicited superior anti-MUC1 IgG titers (3.4M for STn; 2.5M for Tf ELISA units) with predominantly Th1-biased responses (IgG2b: 2.9M STn, 2.4M Tf; IgG2c: 1.7M STn, 0.49M Tf). Induced antibodies demonstrated PDTR region-selective binding, recognized multiple MUC1 glycoforms (Tn, Tf, cores 1-4) while sparing non-MUC1 glycoproteins, with Tf variant inducing broader glycoform recognition than Tn. Antibodies from both constructs bound MUC1-expressing melanoma (B16-MUC1) and breast cancer (MCF-7) cells while showing minimal binding to normal breast cells (MCF-10A), with Tf variant demonstrating superior B16-MUC1 binding (Tf>STn>Tn>unglycosylated) and highest complement-dependent cytotoxicity in vitro. Prophylactic vaccination with Q?-MUC1-Tf significantly reduced lung metastatic tumor burden in a B16-MUC1 challenge model (p=0.008 vs PBS; p=0.003 vs Q?), representing the first MUC1-Tf-based vaccine demonstrating in vivo tumor protection efficacy (Wu et al., 2019).
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| Host Response |
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| References |
Wu et al., 2019: Wu X, McKay C, Pett C, Yu J, Schorlemer M, Ramadan S, Lang S, Behren S, Westerlind U, Finn MG, Huang X. Synthesis and Immunological Evaluation of Disaccharide Bearing MUC-1 Glycopeptide Conjugates with Virus-like Particles. ACS chemical biology. 2019; 14(10); 2176-2184. [PubMed: 31498587].
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