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Vaccine Detail
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MUC1 (144-173)-loaded umbilical cord blood-derived mature DC vaccine |
| Vaccine Information |
- Vaccine Name: MUC1 (144-173)-loaded umbilical cord blood-derived mature DC vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Dendritic cell vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1(144-173) (30 aa, TRPAPGSTAPPAHGVTSAPDTRPAPGSTAP) (Xie et al., 2025)
- Immunization Route: Intradermal injection (i.d.)
- Description: A MUC1 peptide-pulsed umbilical cord blood-derived mature dendritic cell vaccine composed of umbilical cord blood-derived monocytes isolated via Ficoll density gradient centrifugation and differentiated into imDCs using GM-CSF (50 ng/mL) and IL-4 (20 ng/mL) in X-VIVO 15 medium supplemented with 10% inactivated autologous plasma. DCs exhibited peak antigen uptake capacity on day 5 of culture (91.80±2.2% FITC-OVA uptake). On day 5, imDCs were pulsed with MUC1 (144-173) peptide 619 (TRPAPGSTAPPAHGVTSAPDTRPAPGSTAP, 30 aa, 500 ng/mL), an MHC class I-restricted epitope derived from the VNTR domain of MUC1, and matured with LPS and TNF-α (50 ng/mL) to yield mDCs highly expressing CD11c, HLA-DR, CD83, CD80, and CD86 with downregulated CD14 (96.9%→9.94%). CTLs were induced by co-culturing T lymphocytes with DCs at a T:DC ratio of 10:1 with IL-2 (500 IU/mL) for 7 days. The vaccine was administered intradermally at 1×10⁶ cells/50 µL on days 4 and 7 post-tumor implantation in huHSC-M-NSG humanized mice with successful immune reconstitution (hCD45%≥25%). In vitro, the vaccine promoted T lymphocyte proliferation, increased CD8⁺/CD4⁺ ratio in CTLs, and induced IL-12p70 secretion by DCs and IFN-γ secretion by CTLs, with dose-dependent cytotoxicity against pancreatic cancer cell lines (E:T 40:1: 43.4%, 41.8%, 37.8% killing of PANC-1, BXPC-3, MIA PaCa-2), outperforming peptide 568 (MUC1 157-172, GVTSAPDTRPAPGSTA, 16 aa; 32.7%, 30.3%, 29.3%). In vivo, the vaccine achieved 51.4% tumor weight inhibition and 49.6% tumor volume inhibition (d21) compared to 11.15% and 2.30% for unloaded DC controls, with increased peripheral CD8⁺ T cells and enhanced hCD45⁺ tumor infiltration. Three of six vaccinated mice showed tumor weight inhibition rates of 73.0%, 77.5%, and 73.9%. Bioinformatics analysis of TCGA/GTEx data confirmed MUC1 overexpression in pancreatic cancer versus normal tissues (p<0.0001), with high MUC1 expression associated with reduced overall survival (HR=1.58, p=0.041), validated by Western blot in PANC-1, BXPC-3, and MIA PaCa-2 cell lines (Xie et al., 2025).
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| Host Response |
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| References |
Xie et al., 2025: Xie H, Yang W, Chen H, Zhang Z, Zhao Z, Jin Y, Fan S, Yang Z. MUC1 peptide-loaded dendritic cell vaccine boosts antitumor immunity in pancreatic cancer. Frontiers in immunology. 2025; 16; 1752861. [PubMed: 41607777].
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