Effective anti-tumor responses induced by recombinant bacillus Calmette-Guérin vaccines based on different tandem repeats of MUC1 and GM-CSF.

In this study, we constructed several novel breast cancer vaccines, Bacillus Calmette-Guérin (BCG)-MUC1 variable-number tandem repeats (VNTR) 1/4/8-CSF, that consist of BCG and express 1, 4, and 8 of the tandem repeats of MUC1 and human granulocyte-macrophage colony-stimulating factor (GM-CSF). The ability of the three recombinant BCG vaccines to inhibit breast cancer growth was observed in human (hu)-peripheral blood lymphocyte (PBL)-severe combined immunodeficient (SCID) mice. Prophylactic protective responses were successfully induced and the tumor incidence in mice immunized with recombinant BCG (rBCG)-MVNTR4-CSF (37.5%) or rBCG-MVNTR8-CSF (25%) was significantly decreased compared with control (100%) at 42 days after tumor implantation (P<0.05 vs. control group). We also found that CD4-positive and CD8-positive lymphocytes were detected only in tumors grown in rBCG-MVNTR4/8-CSF-immunized animals, and strong IFN-gamma responses were induced by immunization with rBCG-MVNTR4-CSF and rBCG-MVNTR8-CSF vaccines. This study suggests a potential role of coexpressed GM-CSF and tandem repeats of MUC1 in eliciting tumor-specific immune response. Our results indicate that rBCG-MVNTR4-CSF and rBCG-MVNTR8-CSF immunization preventively inhibited breast cancer growth in hu-PBL-SCID mice and the both rBCG vaccines may be good candidates for breast cancer immunotherapy.