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Vaccine Detail
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TRAF6-Overexpressing Bone Marrow-Derived DC Vaccine Loaded with MUC1 Peptide |
| Vaccine Information |
- Vaccine Name: TRAF6-Overexpressing Bone Marrow-Derived DC Vaccine Loaded with MUC1 Peptide
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Dendritic cell vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: 30-mer MUC1 (HGVTSAPDTRPAPGSTAPPAHGVTSAPDTR) (Wang et al., 2022)
- Immunization Route: Intravenous injection (i.v.)
- Description: A lentiviral vector-transduced TRAF6-overexpressing bone marrow-derived dendritic cell (BMDC) vaccine (pLenti-CMV-TRAF6-GFP-Puro), pulsed with a 30-amino acid synthetic MUC1 peptide (HGVTSAPDTRPAPGSTAPPAHGVTSAPDTR) and delivered intravenously in a therapeutic B16-MUC1 subcutaneous melanoma mouse model. TRAF6 overexpression activated downstream AP-1 and NF-κB signaling (upregulated p-ERK, p-IκB, p-JNK), significantly elevated CD40, CD80, CD86, and MHC I expression, with MHC II trending higher but not reaching significance, and increased IL-12p70 secretion 7.9-fold over controls in vitro, driving Th1 polarization evidenced by 4.5-fold higher IFN-γ and decreased IL-4. In vivo, TRAF6+ DCs alone outperformed MUC1-pulsed control DCs in tumor inhibition, with IgG (0.256→0.422), IgG1 (0.173→0.262), IgG2c (0.095→0.283), IgG2c/IgG1 ratio (0.552→1.076), and splenocyte proliferation 1.54-fold over control DCs. TRAF6+ DC + MUC1 produced the strongest tumor inhibition versus all groups, with highest IgG (0.651→1.383), IgG1 (0.348→0.554), IgG2c (0.381→0.746), IgG2c/IgG1 ratio (1.096→1.345), IFN-γ secretion (546.9→965.5 pg/mL), reduced IL-4, splenocyte proliferation (1.20-fold over control DC + MUC1), and CTL killing activity. Vaccination enhanced mature DC accumulation across spleen, lymph nodes, and TME, expanded CD4+ T cells in spleen and lymph nodes, increased CD8+ T cells specifically in TME with no significant difference in spleen or lymph nodes, expanded Th1 1.3-fold in spleen and in lymph nodes for TRAF6+ DC vs control DC, and 1.2-fold for TRAF6+ DC + MUC1 vs control DC + MUC1, expanded Tc1 1.4-fold (TRAF6+ DC vs control DC) and 1.6-fold (TRAF6+ DC + MUC1 vs control DC + MUC1) in lymphoid organs, reduced Tregs in lymph nodes only for TRAF6+ DC + MUC1 vs control DC + MUC1 with no significant lymph node Treg difference between TRAF6+ DC and control DC groups, and significantly reduced Tregs in TME for both comparisons, with no significant Treg difference observed in spleen (Wang et al., 2022).
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| Host Response |
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| References |
Wang et al., 2022: Wang J, Liu Y, Ni W, Wu X, Zhou J, Zhang Z, Zhou H, Zhang N, Jiang M, Sang Q, Yuan H, Tai G. TRAF6-overexpressing dendritic cells loaded with MUC1 peptide enhance anti-tumor activity in B16-MUC1 melanoma-bearing mice. International immunopharmacology. 2022; 107; 108667. [PubMed: 35255300].
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