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Vaccine Detail
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MUC1-Tn-DC-Derived Exosome (Dex) Conjugate Vaccine |
| Vaccine Information |
- Vaccine Name: MUC1-Tn-DC-Derived Exosome (Dex) Conjugate Vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 VNTR (HGVTSAPDTRPAPGSTAPPA) (Zhu et al., 2022)
- Immunization Route: Intraperitoneal injection (i.p.)
- Description: A conjugate vaccine composed of a MUC1 Tn-glycosylated VNTR glycopeptide antigen covalently conjugated to dendritic cell-derived exosomes (Dex, ~105 nm) via a two-step bioorthogonal crosslinking strategy (DBCO-Sulfo-NHS amine coupling followed by copper-free azide-alkyne cycloaddition), yielding ~900 MUC1 molecules per Dex particle and a final conjugate size of ~117 nm. Dex carry endogenous MHC I, MHC II, CD80, CD86, CD40, and DC SIGN, functioning as both carrier and intrinsic adjuvant. In C57BL/6 mice immunized intraperitoneally three times (18 μg/dose, 10-day intervals), MUC1-Dex preferentially targeted dendritic cells over macrophages and neutrophils in spleen and lymph nodes, upregulated CD80, CD86, MHC I, and MHC II on BMDCs to levels comparable to LPS, and induced the highest MUC1-specific IgG titers with a Th1-biased isotype profile (IgG2b > IgG1) and significantly elevated IL-2, IFN-γ, and TNF-α secretion with modest increases in IL-4 and IL-5. Antisera bound strongly to MUC1-expressing MCF-7 cells and demonstrated the strongest complement-dependent cytotoxicity. At 100:1 effector-to-target ratio, MUC1-Dex-primed CD8+ T cells lysed ~35% of MCF-7 cells, double the MUC1 group and triple the Dex-alone group. In a therapeutic B16-MUC1 melanoma model, MUC1-Dex reduced tumor volume to 252 mm³ by day 21 versus 694 mm³ (MUC1+Dex) and 1,403 mm³ (MUC1 alone), extending survival to 55 days versus 25-30 days for all other groups. In a prophylactic model, 40% of MUC1-Dex mice remained tumor-free through day 31, and tumor-free mice rechallenged with B16-MUC1 on day 51 remained tumor-free through end of observation, demonstrating durable immunological memory (Zhu et al., 2022).
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| Host Response |
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| References |
Zhu et al., 2022: Zhu H, Wang K, Wang Z, Wang D, Yin X, Liu Y, Yu F, Zhao W. An efficient and safe MUC1-dendritic cell-derived exosome conjugate vaccine elicits potent cellular and humoral immunity and tumor inhibition in vivo. Acta biomaterialia. 2022; 138; 491-504. [PubMed: 34757230].
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