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Vaccine Detail
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Recombinant MUC1-Maltose-Binding Protein (MBP) fusion protein vaccine |
| Vaccine Information |
- Vaccine Name: Recombinant MUC1-Maltose-Binding Protein (MBP) fusion protein vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Subunit vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: 22 MUC1 VNTRs; Maltose binding protein (MBP) (Zhou et al., 2020; Liu et al., 2022; Liu et al., 2023)
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Adjuvant:
CpG ODN 2006 (Zhou et al., 2020; Liu et al., 2022; Liu et al., 2023)
- Immunization Route: subcutaneous injection
- Description: A recombinant fusion protein vaccine comprising full-length human Mucin-1 (MUC1) with 22 tandem repeats (TRs) fused with Escherichia coli maltose-binding protein (MUC1-MBP), adjuvanted with the human-compatible TLR9 agonist CpG ODN 2006. MBP activates NK cells, macrophages (M1 polarization), and DCs via TLR2/TLR4 signaling, while CpG2006 activates TLR9-MyD88-NF-κB and TLR9-MyD88-IRF7 pathways to amplify immune responses. In a prophylactic B16-MUC1 subcutaneous melanoma mouse model, five immunizations (25–100 µg, subcutaneous, 7-day intervals) achieved tumor inhibition rates of 71.9–82.9% in a dose-dependent manner, with 100-day survival rates of 10–40% across dose groups versus 0% in controls, and MUC1-specific CTL killing of 73.39% at E:T 50:1 versus 17.79% with MUC1-MBP alone (Liu et al., 2022). The vaccine induced Th1-biased immunity with an IgG2c/IgG1 ratio of 1.88 after five immunizations versus 1.26 after eight immunizations, Th1 and Tc1 populations elevated 1.83- and 1.72-fold respectively, MDSCs reduced 8.52-fold in spleen with CD8+/MDSC ratio increased 6.51-fold versus 1.37-fold after eight immunizations, and increased CD4+ and CD8+ T cell infiltration in the TME (Zhou et al., 2020). Mechanistically, cDC1s (CD11c+CD8α+pDCA1−) were identified as the primary cross-presenting subset, with type I IFN signaling through IFNAR1 on cDC1s as a critical regulatory axis; global IFNAR1 blockade reduced CTL killing by 61.9% and selective cDC1 blockade by 55.63% (Liu et al., 2022). Optimal efficacy was observed at five immunization cycles; beyond five cycles, tumor inhibition declined from 81.67% to 43.67%, accompanied by progressive DC PD-L1 upregulation and Treg expansion (Zhou et al., 2020; Liu et al., 2023). Combination with anti-PD-L1 antibody (200 µg) reversed tolerance by downregulating DC PD-L1 by 47–60% predominantly in cDC1s, restoring Th1/Tc1 activity, increasing TME CD8+ T cell infiltration, and reducing Treg frequency and IL-10 production (Liu et al., 2023).
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| Host Response |
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| References |
Liu et al., 2022: Liu Y, Zhang Z, Sang Q, Zhang Y, Jiang M, Zhou H, Wang J, Zhang N, Wu X, Zhou J, Ni W, Yuan H, Tai G. Recombinant MUC1-MBP fusion protein combined with CpG2006 vaccine induces antigen-specific CTL responses through cDC1-mediated cross-priming mainly regulated by type I IFN signaling in mice. Immunology letters. 2022; 245; 38-50. [PubMed: 35405170].
Liu et al., 2023: Liu G, Zhang Z, Wu Y, Feng J, Lan Y, Dong D, Liu Y, Yuan H, Tai G, Li S, Ni W. Anti-PD-L1 antibody reverses the immune tolerance induced by multiple MUC1-MBP vaccine immunizations by increasing the CD80/PD-L1 ratio, resulting in DC maturation, and decreasing Treg activity in B16-MUC1 melanoma-bearing mice. International immunopharmacology. 2023; 121; 110487. [PubMed: 37364328].
Zhou et al., 2020: Zhou H, Zhang Z, Liu G, Jiang M, Wang J, Liu Y, Tai G. The Effect of Different Immunization Cycles of a Recombinant Mucin1-Maltose-Binding Protein Vaccine on T Cell Responses to B16-MUC1 Melanoma in Mice. International journal of molecular sciences. 2020; 21(16); . [PubMed: 32823603].
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