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.
Yuan
Shifang
S
Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, PR China. shifangy@fmmu.edu.cn
Shi
Changhong
C
Han
Wei
W
Ling
Rui
R
Li
Nanlin
N
Wang
Ting
T
D000818:Animals; D001500:BCG Vaccine / Q000235:genetics / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology / Q000517:prevention & control*; D019496:Cancer Vaccines / Q000235:genetics; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D018396:Mucin-1 / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D020080:Tandem Repeat Sequences; D019444:Vaccines, DNA / Q000276:immunology
D001500:BCG Vaccine; D019496:Cancer Vaccines; C060192:MUC1 protein, human; D018396:Mucin-1; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor