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Vaccine Detail
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CpG-containing double-cassette vector (CpDV) DNA vaccine co-expressing IL-2 and soluble PD-1/MUC1-survivin [CpDV-IL2-sPD1/MS] |
| Vaccine Information |
- Vaccine Name: CpG-containing double-cassette vector (CpDV) DNA vaccine co-expressing IL-2 and soluble PD-1/MUC1-survivin [CpDV-IL2-sPD1/MS]
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: DNA vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: 33 MUC1 VNTRs; survivin (S8) (Liu et al., 2018)
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Adjuvant:
sPD1 (molecular adjuvant), CpG motifs, IL-2 (Liu et al., 2018)
- Immunization Route: Intramuscular injection (i.m.)
- Description: A fusion DNA vaccine (CpDV-IL2-sPD1/MS) co-expressing soluble PD-1 (sPD-1, extracellular domain only) fused with human MUC1 VNTRs (33 repeats) and truncated survivin S8, with IL-2 in a separate cassette, CpG motifs in the vector backbone, and a tPA signal sequence for enhanced secretion, delivered intramuscularly in a DNA prime / recombinant adenovirus boost regimen. sPD-1 targets PD-L1/PD-L2 on dendritic cells to facilitate antigen uptake and MHC class I cross-presentation, enhancing CD8+ T cell activation against MUC1- and survivin-expressing tumor cells. Compared to MS vaccine alone, sPD1/MS upregulated DC maturation markers (CD80, CD86, IL-12p35, IL-12p40), T cell effector markers (Granzyme B, PD-L1), and CD4+CD69+/CD8+CD69+ splenocyte populations, increased IFN-γ secretion, specific cytolysis from 21.64% to 34.77% and 30.39% to 35.56%, and raised anti-MUC1/survivin titers 8-10-fold (p<0.001) with elevated IgG1 (~1.6-fold) and IgG2a (~1.7-fold); tumor-bearing mice showed IgG1 predominance indicating Th2 skewing. In a murine colorectal cancer model (MSf+-CT26), tumor suppression increased from 17.18% to 30.96%, survival from 6.96% to 19.44% (p<0.05), and median survival prolonged 2.8-fold vs MS. Combining with oxaliplatin raised tumor suppression to 74.71% (2.4-fold over sPD1/MS, p<0.001; 27.45% over oxaliplatin alone at 58.62%, p<0.05) with GrzB, Prf1 and IFN-γ upregulated and PD-L1 upregulated 2-3-fold. In a murine lung cancer model (MSf+-Lewis), 80% survived to day 90 vs. 0% of controls by day 52 (p<0.001), tumor growth suppressed days 23–27, cytolysis increased >4-fold, IFN-γ-secreting lymphocytes increased ~3-fold, tumor-infiltrating CD8+ T cells increased 6.5-fold (0.10% to 0.65%, p<0.001), and intratumoral Tregs decreased 28.67% (7.57% to 5.4%)(Liu et al., 2018).
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| Host Response |
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| References |
Liu et al., 2018: Liu C, Lu Z, Xie Y, Guo Q, Geng F, Sun B, Wu H, Yu B, Wu J, Zhang H, Yu X, Kong W. Soluble PD-1-based vaccine targeting MUC1 VNTR and survivin improves anti-tumor effect. Immunology letters. 2018; 200; 33-42. [PubMed: 29894719].
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