• Vaccine Name: pCEP4-MUC1 cDNA Plasmid DNA Vaccine
• Target Pathogen: Cancer
• Target Disease: Cancer
• Vaccine Ontology ID: VO_0004437
• Type: DNA vaccine
• Status: Research
• Host Species for Licensed Use: Mouse
• Host Species as Laboratory Animal Model: Mouse
• Antigen: Full-length MUC1 cDNA (22 VNTRs; each VNTR 20 aa) (Kamata et al., 2002)
• Muc1 gene engineering:
  • Type: Recombinant protein preparation
  • Description: (Kamata et al., 2002)
  • Detailed Gene Information: Click Here.
• DNA vaccine plasmid: pCEP4 DNA vaccine plasmid
  • DNA vaccine plasmid name: pCEP4 DNA vaccine plasmid
  • DNA vaccine plasmid VO ID: VO_0000175
• Preparation: The vaccine consisted of purified pCEP4 plasmid DNA containing full-length MUC1 cDNA (22 tandem repeats) (Kamata et al., 2002).
• Immunization Route: Intradermal injection (i.d.)
• Description: A plasmid DNA vaccine consisting of full-length human MUC1 cDNA (22 tandem repeats) cloned into the pCEP4 expression vector under the CMV promoter, administered intradermally into C57BL/6 mice. Three weekly intradermal injections of 25 µg pCEP4-MUC1 generated MUC1-specific serum antibodies only becoming significant after the 3rd dose, comprising IgG1, IgG2a, IgG2b, IgG3, IgA, and IgM isotypes with IgG2b predominant, reactive against synthetic 29-mer MUC1 tandem repeat peptide, fully glycosylated HMFG, and F10-MUC1-C8 melanoma cells, with titers correlating with plasmid dose. No MUC1-specific CTL activity was detectable by 51Cr-release assay even after in vitro restimulation, and no ADCC activity was detected. In experimental lung metastasis challenge with F10-MUC1-C8 cells, three immunizations produced significantly lower lung metastatic nodules compared to pCEP4 vector controls (p<0.001), in an antigen-specific manner with no suppression observed against MUC1-negative F10-mock-C4 cells. Protection was dose-dependent (p<0.05) with no suppression at 0.5 µg, while doses of 2.5-50 µg all resulted in reduced lung metastases compared to vector controls, and required three immunizations as a single dose was insufficient. In vivo lymphocyte depletion identified NK1.1+ cells as the primary effector population with complete abrogation of metastasis suppression upon NK depletion (p<0.001), while CD4+ and CD8+ depletion produced only partial abrogation (p<0.01 and p<0.05 respectively) (Kamata et al., 2002).

Mouse Response

• Vaccine Immune Response Type: VO_0000286
• Immune Response: Humoral immune responses specific for MUC1 were induced. Antibody binding to HMFG and F10-MUC1-C8 cells was usually detected after 3 immunizations, indicating that MUC1 DNA vaccination elicited a humoral immune response, with antibodies reacting to glycosylated MUC1 and F10-MUC1-C8 cells. The suppression of lung metastasis was primarily mediated by NK cells, which completely abrogated the suppressive effect of MUC1 DNA vaccination upon depletion, but CD4+ cells and CD8+ cells may also play a role. Mice treated with anti-CD4 or anti-CD8 antibodies showed only partial abrogation of the vaccine's suppressive effect. CTL and ADCC activities were not detectable (Kamata et al., 2002).
• Efficacy: The number of lung metastatic nodules three weeks after inoculation of F10-MUC1-C8 cells was significantly lower in mice immunized with pCEP4-MUC1 DNA vaccine 3 times at weekly intervals than in mice immunized with the vector DNA alone or with a single immunization of the DNA vaccine (Kamata et al., 2002).