Immunization with two recombinant Bacillus Calmette-Guérin vaccines that combine the expression of multiple tandem repeats of mucin-1 and colony stimulating-factor suppress breast tumor growth in mice.
OBJECTIVE
Mucin-1 (MUC1) is a breast tumor-associated antigen. However, clinical trials with MUC1 showed that, with respect to its expression levels, MUC1 is a relatively poor immunogen in human beings. Evidence showed that MUC1-specific immunodominant B and T cell epitopes are derived from the variable-number tandem repeat (VNTR) region. Therefore, immunotherapy that targets multiple VNTRs may induce anti-MUC1 immune responses. GM-CSF has been shown to increase the percentage and activity of antigen-presenting cells. In this study, we constructed two recombinant Bacillus Calmette-Guérin (BCG) vaccines that combine the expression of multiple tandem repeats of MUC1 and CSF. The effect of two novel breast cancer vaccines (rBCG-MVNTR4-CSF and rBCG-MVNTR8-CSF) on the growth of breast tumor on hu-PBL-SCID mice was evaluated.


METHODS
We coupled VNTRs (4 and 8) of MUC1 with GM-CSF (MVNTR4-CSF and MVNTR8-CSF). The MVNTR4-CSF and MVNTR8-CSF were inserted into the pDE22 plasmid and transformed into competent BCG by electroporation. The effect of both BCG vaccines on the growth of breast tumor on hu-PBL-SCID mice was evaluated.


RESULTS
The growth of MUC1-positive breast tumors from hu-PBL-SCID mice immunized with two vaccines was significantly inhibited.


CONCLUSIONS
rBCG-MVNTR4-CSF and rBCG-MVNTR8-CSF vaccines may be good candidates for breast tumor immunotherapy.
Yuan
Shifang
S
Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, 17 Changle West Road, Xi'an, 710033, People's Republic of China.
Shi
Changhong
C
Ling
Rui
R
Wang
Ting
T
Wang
Hui
H
Han
Wei
W
D000818:Animals; D001500:BCG Vaccine / Q000235:genetics* / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D018598:Minisatellite Repeats / Q000235:genetics; D018396:Mucin-1 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000627:therapeutic use
D001500:BCG Vaccine; D019496:Cancer Vaccines; C060192:MUC1 protein, human; D018396:Mucin-1; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor