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Vaccine Detail
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MUC1 9mer (Glyco)peptide Vaccines (APG, SAP, APG-Tn, SAP-Tn) |
| Vaccine Information |
- Vaccine Name: MUC1 9mer (Glyco)peptide Vaccines (APG, SAP, APG-Tn, SAP-Tn)
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: (Glyco)peptide vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 (Lakshminarayanan et al., 2016)
- Immunization Route: subcutaneous injection
- Description: A synthetic peptide vaccine containing short 9-amino acid MUC1-derived peptides (APG 9mer: APGSTAPPA; SAP 9mer: SAPDTRPAP) in both non-glycosylated and Tn-glycosylated forms (APG-Tn, SAP-Tn), adjuvanted with CpG 1826 oligonucleotide and Incomplete Freund's Adjuvant (IFA). The peptides are derived from the MUC1 tandem repeat (TR) region and correspond to H-2Db (APG) and H-2Kb (SAP) restricted epitopes. Vaccination generates increased CD4+ and CD8+ interferon-gamma producing T-cell responses with maximal avidity that demonstrate cross-recognition of both glycosylated and non-glycosylated MUC1 antigens, including tumor-associated MUC1, as well as intramolecular epitope spreading from the tandem repeat to cytoplasmic tail domains. The Tn glycosylation (?GalNAc O-linked to serine/threonine) mimics aberrant tumor-associated glycosylation patterns. In prophylactic settings, vaccination prior to B16.MUC1 tumor challenge provided 0% protection but induced immunoediting with decreased tumor MUC1 and MHC expression. Therapeutic vaccination continued post-tumor challenge achieved 30% complete tumor eradication (3/10 mice) with significant tumor growth delay (p=0.001). MUC1 is a membrane-bound glycoprotein overexpressed in an aberrant or underglycosylated form in approximately 75% of lethal human cancers including breast, pancreatic, and ovarian cancers (Lakshminarayanan et al., 2016).
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| Host Response |
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| References |
Lakshminarayanan et al., 2016: Lakshminarayanan V, Supekar NT, Wei J, McCurry DB, Dueck AC, Kosiorek HE, Trivedi PP, Bradley JM, Madsen CS, Pathangey LB, Hoelzinger DB, Wolfert MA, Boons GJ, Cohen PA, Gendler SJ. MUC1 Vaccines, Comprised of Glycosylated or Non-Glycosylated Peptides or Tumor-Derived MUC1, Can Circumvent Immunoediting to Control Tumor Growth in MUC1 Transgenic Mice. PloS one. 2016; 11(1); e0145920. [PubMed: 26788922].
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