1. 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.
- Author
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Shifang Yuan, Changhong Shi, Yonggang Lv, Ting Wang, Hui Wang, and Wei Han
- Subjects
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BCG vaccines , *BREAST cancer vaccines , *CANCER immunotherapy , *GENE expression , *INTERFERONS , *LABORATORY mice ,TUMOR growth prevention - Abstract
AbstractMany 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. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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