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Vaccine Detail
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pVAX1-MUC1-6VNTR DNA Vaccine with C-terminal PDTRP Positioning |
| Vaccine Information |
- Vaccine Name: pVAX1-MUC1-6VNTR DNA Vaccine with C-terminal PDTRP Positioning
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: DNA vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 (Gong et al., 2017)
- Immunization Route: Intramuscular injection (i.m.)
- Description: A plasmid DNA vaccine encoding six tandem repeats of the mucin 1 variable number tandem repeat (MUC1-VNTR) region with C-terminal PDTRP positioning for enhanced immunogenicity, constructed in the pVAX1 mammalian expression vector. Upon intramuscular administration, the plasmid DNA is taken up by host cells, which then express the MUC1-6VNTR protein and present it to the immune system, eliciting both humoral and cytotoxic T-lymphocyte (CTL) responses against MUC1-positive tumor cells. The vaccine design features strategic positioning of the PDTRP pentapeptide sequence at the C-terminus of each VNTR unit, which confers stronger immunogenicity compared to N-terminal positioning. In preclinical studies, VNTR6 demonstrated the highest IFN-γ-producing CTL counts (105.2±8.7 vs 16.8±4.8 for empty vector; P<0.001) and strongest cytotoxicity against MUC1-positive Capan2 pancreatic cancer cells (41.25±3.34% vs 2.46±1.87% for control; P<0.001). The vaccine induced robust dendritic cell maturation with increased expression of CD80, CD86, and HLA-DR surface markers, elevated IL-12, IFN-γ, and IL-17 secretion, and superior tumor growth inhibition in mouse models compared to other VNTR variants (P<0.01). MUC1 antigen is a membrane-bound glycoprotein that is overexpressed in underglycosylated form in approximately 90% of pancreatic cancers and various other adenocarcinomas, making it a promising target for cancer immunotherapy (Gong et al., 2017).
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| Host Response |
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| References |
Gong et al., 2017: Gong YF, Zhou QB, Liao YD, Mai C, Chen TJ, Tang YQ, Chen RF. Optimized construction of MUC1-VNTR(n) DNA vaccine and its anti-pancreatic cancer efficacy. Oncology letters. 2017; 13(4); 2198-2206. [PubMed: 28454381].
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