A novel Bacillus Calmette-Guérin-based breast cancer vaccine that coexpresses multiple tandem repeats of MUC1 and CD80 breaks the immune tolerance and inhibits MUC1-positive breast cancer growth.
Many approaches targeting MUC1 for breast tumor immunotherapy have been attempted. However, preclinical trials with MUC1 showed that MUC1 is a relatively poor immunogen in human. B7 molecules that bind CD28 provide an antigen-nonspecific signal, which, along with an antigen-specific signal, is crucial for T-cell activation. In the present study, we constructed a novel Bacillus Calmette-Guérin-based breast cancer vaccine that coexpressed four VNTRs (variable-number tandem repeats) of MUC1 and CD80 (rBCG-MVNTR4-CD80). The aim of our study was to enhance anti-MUC1 tumor immunity by vaccination of hu-PBL-SCID mice with the recombinant BCG vaccine. The inhibition effect on tumors from the mice immunized with rBCG-MVNTR4-CD80 significantly increased, compared with rBCG-MVNTR4, BCG-pDE22, and phosphate-buffered saline immunized mice (p < 0.05, p < 0.05, p < 0.05). ELISpot assays showed that there was a significant increase in interferon-gamma production in the splenocytes from the mice immunized with rBCG-MVNTR4-CD80. In addition, CD4 and CD8-positive lymphocytes in tumors from rBCG-MVNTR4-CD80-immunized animals were detected. These data showed that rBCG-MVNTR4-CD80 immunization elicited tumor-specific immune response, which closely related with the B7 molecule (CD80), indicating that the vaccine may be a good candidate for MUC1-positive breast cancer immunotherapy.
Yuan
Shifang
S
Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Shi
Changhong
C
Lv
Yonggang
Y
Wang
Ting
T
Wang
Hui
H
Han
Wei
W
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics*; D001500:BCG Vaccine / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005260:Female; D007107:Immune System; D007108:Immune Tolerance; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D018396:Mucin-1 / Q000235:genetics*; D016896:Treatment Outcome
D018122:B7-1 Antigen; D001500:BCG Vaccine; D019496:Cancer Vaccines; C060192:MUC1 protein, human; D018396:Mucin-1; D007371:Interferon-gamma