Journal of Cancer Research and Clinical Oncology

, Volume 136, Issue 9, pp 1359–1367

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

Authors

  • Shifang Yuan
    • Department of Vascular and Endocrine SurgeryXijing Hospital, Fourth Military Medical University
  • Changhong Shi
    • Laboratory Animal Research Center of the Fourth Military Medical University
  • Rui Ling
    • Department of Vascular and Endocrine SurgeryXijing Hospital, Fourth Military Medical University
  • Ting Wang
    • Department of Vascular and Endocrine SurgeryXijing Hospital, Fourth Military Medical University
  • Hui Wang
    • Department of Vascular and Endocrine SurgeryXijing Hospital, Fourth Military Medical University
    • Biotechnology Center of the Fourth Military Medical University
Original Paper

DOI: 10.1007/s00432-010-0787-x

Cite this article as:
Yuan, S., Shi, C., Ling, R. et al. J Cancer Res Clin Oncol (2010) 136: 1359. doi:10.1007/s00432-010-0787-x

Abstract

Purpose

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.

Keywords

MUC1Variable-number tandem repeatRecombinant BCG vaccineBreast tumorAnti-tumor immunotherapy

Abbreviations

SCID

Severe combined immunodeficient

BCG

Bacillus Calmette-Guérin

cfu

Colony-forming unit(s)

VNTR

Variable-number tandem repeat

ATCC

American type culture collection

PBL

Peripheral blood lymphocyte

GM-CSF

Granulocyte–macrophage colony stimulating factor

Copyright information

© Springer-Verlag 2010