• Vaccine Name: Recombinant Vaccinia-MUC1-B7 Vaccine
• Target Pathogen: Cancer
• Target Disease: Cancer
• Vaccine Ontology ID: VO_0007040
• Type: Recombinant vector vaccine
• Status: Research
• Host Species for Licensed Use: Mouse
• Host Species as Laboratory Animal Model: Human
• Antigen: 10 MUC1 VNTRs (Akagi et al., 1997)
• MUC1 gene engineering:
  • Type: Recombinant protein preparation
  • Description: (Akagi et al., 1997)
  • Detailed Gene Information: Click Here.
• Cd80 gene engineering:
  • Type: Recombinant protein preparation
  • Description: (Akagi et al., 1997)
  • Detailed Gene Information: Click Here.
• Preparation: rV-MUC1 was admixed with a recombinant vaccinia virus containing the gene for the murine T-cell costimulatory molecule B7-1 (rV-B7). rV-MUC1 was constructed containing a modified "mini" MUC1 gene containing only 10 tandem repeat sequences to minimize vaccinia-mediated rearrangement (Akagi et al., 1997).
• Immunization Route: subcutaneous injection
• Description: A recombinant vaccinia virus-based admixture vaccine comprising rV-MUC1, encoding a modified "mini" MUC1 gene with only 10 tandem repeat sequences to minimize vaccinia-mediated rearrangement, and rV-B7, encoding the murine T-cell costimulatory molecule B7-1. This is for breast cancer, ovarian cancer, lung cancer, pancreatic cancer, and colorectal cancer (NCIT_C29409, Ref3895:Akagi et al., 1997) MUC-1 is a glycosylated mucin overexpressed in breast, lung, pancreatic, prostate, stomach, colon, and ovarian carcinomas; vaccination with MUC-1 in combination with B7.1 may enhance the CTL immune response to MUC-1-expressing tumors compared to MUC-1 alone (NCI04) (NCIT_C29409). The miMUC1 gene product maintained stable expression across five viral passages, producing a consistent 150–175 kDa glycoprotein confirmed by Western blot using DF3 monoclonal antibody. MC38/MUC1 cells demonstrated strong surface MUC1 expression (87.5% DF3-positive, mean fluorescence intensity of 40) and were confirmed negative for B7-1 expression, ensuring any costimulatory effect was solely attributable to rV-B7. Inoculation of C57BL/6 mice with rV-MUC1 elicited MUC1-specific CTL lysis (~12% at 100:1 E:T, declining to ~7% at 12.5:1), further enhanced by admixture with rV-B7 (peaking ~17% at 50:1, declining to ~5% at 12.5:1), with MUC1-negative targets showing ~1-2% lysis confirming specificity. In a pulmonary metastases prevention model, two immunizations with rV-MUC1 (with or without rV-B7 in the priming dose) protected 90% of mice from establishment of metastases following intravenous challenge with 1×10⁶ MC38/MUC1 tumor cells. In a therapeutic setting with established metastases, three immunizations with rV-MUC1/V-Wyeth alone were insufficient, with 7 of 10 mice having <50 nodules and 80% eventually succumbing to tumor; controls (V-Wyeth and rV-B7/V-Wyeth) had 9 of 10 and 7 of 10 mice with >250 nodules respectively. In contrast, priming with rV-MUC1 + rV-B7 admixture followed by two rV-MUC1/V-Wyeth boosts produced a significant reduction in pulmonary metastases (p<0.0001), with 30% of mice completely free of metastases and remaining mice having <20 nodules, correlating with 100% survival at day 65 and significant survival improvement (p=0.0009-<0.0001) compared to controls, which showed 100% mortality by days 50–56. Coexpression of B7 was not necessary for prevention but was essential in the therapeutic setting (Akagi et al., 1997) (Akagi et al., 1997).

Human Response