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

  • Shifang Yuan
  • Changhong Shi
  • Rui Ling
  • Ting Wang
  • Hui Wang
  • Wei Han
Original Paper

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

MUC1 Variable-number tandem repeat Recombinant BCG vaccine Breast tumor Anti-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

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Shifang Yuan
    • 1
  • Changhong Shi
    • 2
  • Rui Ling
    • 1
  • Ting Wang
    • 1
  • Hui Wang
    • 1
  • Wei Han
    • 3
  1. 1.Department of Vascular and Endocrine SurgeryXijing Hospital, Fourth Military Medical UniversityXi’anPeople’s Republic of China
  2. 2.Laboratory Animal Research Center of the Fourth Military Medical UniversityXi’anPeople’s Republic of China
  3. 3.Biotechnology Center of the Fourth Military Medical UniversityXi’anPeople’s Republic of China

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