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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

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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.

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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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Acknowledgments

This work was supported by a grant from the National Natural Science Foundation of China (No. 30571802). We thank Professor Li YUAN (Department of Microbiology, Fourth Military Medical University, Xi’an, China) for kindly providing the E. coli-BCG shuttle vector pDE22.

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Correspondence to Wei Han.

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Yuan, S., Shi, C., Ling, R. et al. 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. J Cancer Res Clin Oncol 136, 1359–1367 (2010). https://doi.org/10.1007/s00432-010-0787-x

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  • DOI: https://doi.org/10.1007/s00432-010-0787-x

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