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Vaccine Detail
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TLR7 Agonist (SZU101)-Conjugated MUC1 Peptide Vaccine |
| Vaccine Information |
- Vaccine Name: TLR7 Agonist (SZU101)-Conjugated MUC1 Peptide Vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 (Liu et al., 2020)
- Immunization Route: Intraperitoneal injection (i.p.)
- Description: A synthetic peptide conjugate vaccine composed of a novel TLR7 agonist (SZU101) covalently linked to a murine MUC1 peptide epitope at a 3:1 molar ratio via lysine linker to the N-terminus, synthesized using solid-phase Fmoc strategy. The self-adjuvanting design integrates the TLR7 agonist for innate immune activation with the unglycosylated MUC1 peptide as the tumor-associated antigen. In the 4T1 mouse breast cancer model, three intraperitoneal vaccinations (28 μg on days 0, 14, 28) followed by tumor challenge on day 21 achieved ≥70% tumor weight reduction compared to controls (mean control tumor weight: 0.75±0.10 g) with significantly prolonged survival over 50-day observation (p<0.05). The vaccine elicited robust humoral immunity with high anti-MUC1 antibody titers (IgG: 11,147; IgM: 9,552; IgG1: 12,890; IgG2a: 13,257) and Th1-biased cellular immunity with significantly elevated CD3+/CD8+ T-cell percentages and enhanced cytotoxic T-lymphocyte (CTL) and antibody-dependent cell-mediated cytotoxicity (ADCC) activity against 4T1 tumor cells. In vitro studies demonstrated concentration-dependent (0.1-100 μg/ml) cytokine release (IL-12, TNF-α, IFN-γ) from mouse bone marrow dendritic cells and spleen lymphocytes. Human DC-CIK co-culture experiments confirmed MUC1-dependent selectivity with significant cytotoxicity against high MUC1-expressing MCF-7 cells but not against MUC1-low K562 or MUC1-negative MB231 cells. The conjugate design proved superior to simple mixtures or individual components alone (T7 or MUC1), demonstrating synergistic antitumor effects. MUC1 is a membrane-associated glycoprotein upregulated in >70% of all cancers with critical roles in tumorigenicity and tumor progression (Liu et al., 2020).
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| References |
Liu et al., 2020: Liu Y, Tang L, Gao N, Diao Y, Zhong J, Deng Y, Wang Z, Jin G, Wang X. Synthetic MUC1 breast cancer vaccine containing a Toll-like receptor 7 agonist exerts antitumor effects. Oncology letters. 2020; 20(3); 2369-2377. [PubMed: 32782554].
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