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Vaccine Detail
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Heterologous DNA Prime/rMVA Boost Vaccine Co-targeting MUC1 and Survivin Combined with Metformin [3D/M+Met] |
| Vaccine Information |
- Vaccine Name: Heterologous DNA Prime/rMVA Boost Vaccine Co-targeting MUC1 and Survivin Combined with Metformin [3D/M+Met]
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: DNA vaccine/recombinant viral vector
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1; survivin (Guo et al., 2024)
- Immunization Route: Intramuscular injection (i.m.)
- Description: A heterologous prime-boost cancer vaccine co-targeting MUC1 and survivin, consisting of three intramuscular DNA vaccine administrations within one week (100 µg per mouse, tibialis anterior) followed by a single recombinant Modified Vaccinia Ankara (rMVA) boost (5×10⁷ PFU) one week later (3D/M strategy), combined with continuous metformin administration (300 mg/kg, intragastric gavage). The DNA and rMVA vaccines co-target MUC1 and survivin. Previously validated in an MSf⁺ Lewis lung cancer model; tested here in MSf⁺B16 melanoma tumor-bearing C57BL/6J mice, with treatment beginning day 4 after tumor inoculation. 3D/M alone: 64.7% tumor inhibition vs 41.6% (DNA) vs 37.5% (3rMVA); mean survival 47d vs 38d (DNA) vs 38d (3rMVA). Metformin alone: 44.6% tumor inhibition; survival +23.0% vs vehicle [from a separate preliminary experiment; in the combination experiment, the Met arm showed 30.3% inhibition]. Combination (3D/M+Met): 77.4% tumor inhibition vs 52.2% (3D/M) vs 30.3% (Met); mean survival 50d vs 42.5d (3D/M) vs 37d (Met) vs 32d (vehicle). CD4⁺ and CD8⁺ T cell infiltration increased in all groups, highest in combination. CD4⁺Ki67⁺/CD8⁺Ki67⁺: 12.2%/9.2% (combination) vs 6.3%/4.9% (3D/M) vs 9.5%/6.1% (Met) vs 5.5%/3.2% (vehicle). 3D/M alone did not reduce T cell exhaustion or apoptosis. CD4⁺PD-1⁺/CD8⁺PD-1⁺: 3.4%/4.5% (combination) vs 4.9%/4.7% (Met) vs 11.7%/9.8% (3D/M). CD4⁺AnnexinV⁺/CD8⁺AnnexinV⁺: 3.3%/2.5% (combination) vs 3.6%/3.4% (Met) vs 14.1%/7.3% (3D/M). M1-TAM increased and M2-TAM decreased in Met and combination groups. Treg decreased in the CD4⁺ gate, greatest in combination, but was unchanged in the CD45⁺ gate. MDSCs were unaffected. Gzmb, IFN-γ, IL-2, and TNF-α mRNA showed moderate increases with Met or 3D/M alone and were highest in combination. MUC1- and survivin-specific IFN-γ ELISpot: Combination > 3D/M > Met > Vehicle. Met alone generated antigen-specific responses likely through MUC1/survivin antigen release from metformin-induced tumor-cell death. PD-L1 mRNA was reduced in Met and combination groups vs vehicle and 3D/M. Metformin reduced PD-L1 protein in vitro concentration-dependently (MFI: 8.6×10³ at 0 µM → 5.4×10³ at 2.5 µM → 3.3×10³ at 5 µM). No major cell viability effect at 0–500 µM; inhibition only at 5 mM. Tumor metformin was estimated to remain in the µM range after intragastric administration, consistent mainly with immunomodulation rather than direct cytotoxicity (Guo et al., 2024).
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| Host Response |
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| References |
Guo et al., 2024: Guo Q, Wang L, Wuriqimuge, Dong L, Feng M, Bao X, Zhang K, Cai Z, Qu X, Zhang S, Wu J, Wu H, Wang C, Yu X, Kong W, Zhang H. Metformin improved a heterologous prime-boost of dual-targeting cancer vaccines to inhibit tumor growth in a melanoma mouse model. International immunopharmacology. 2024; 128; 111431. [PubMed: 38244520].
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