Mage-b vaccine delivered by recombinant Listeria monocytogenes is highly effective against breast cancer metastases

S. H. Kim, F. Castro, D. Gonzalez, P. C. Maciag, Y. Paterson, Claudia Gravekamp

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

New therapies are needed that target breast cancer metastases. In previous studies, we have shown that vaccination with pcDNA3.1-Mage-b DNA vaccine is effective against breast cancer metastases. In the study presented here, we have further enhanced the efficacy of Mage-b vaccination through the improved delivery of the vaccine using recombinant Listeria monocytogenes (LM). Three overlapping fragments of Mage-b as well as the complete protein-encoding region of Mage-b have been expressed as a fusion protein with a truncated non-cytolytic form of listeriolysin O (LLO) in recombinant LM. These different Mage-b vaccine strains were preventively tested for their efficacy against breast cancer metastases in a syngeneic mouse tumour model 4T1. The LM-LLO-Mage-b/2nd, expressing position 311-660 of the cDNA of Mage-b, was the most effective vaccine strain against metastases in the 4T1 mouse breast tumour model. Vaccination with LM-LLO-Mage-b/2nd dramatically reduced the number of metastases by 96% compared with the saline group and by 88% compared with the vector control group (LM-LLO), and this correlated with strong Mage-b-specific CD8 T-cell responses in the spleen, after restimulation with Mage-b. However, no effect of LM-LLO-Mage-b/2nd was observed on 4T1 primary tumours, which may be the result of a complete absence of Mage-b-specific immune responses in the draining lymph nodes. Vaccination with LM-LLO-Mage-b/2nd could be an excellent follow-up after removal of the primary tumour, to eliminate metastases and residual tumour cells.

Original languageEnglish (US)
Pages (from-to)741-749
Number of pages9
JournalBritish Journal of Cancer
Volume99
Issue number5
DOIs
StatePublished - Sep 2 2008

Fingerprint

Synthetic Vaccines
Listeria monocytogenes
Breast Neoplasms
Neoplasm Metastasis
Vaccination
Vaccines
Neoplasms
DNA Vaccines
Residual Neoplasm
Listeria monocytogenes hlyA protein
Proteins
Spleen
Complementary DNA
Lymph Nodes
T-Lymphocytes
Control Groups

Keywords

  • 4T1 model
  • Breast cancer metastases
  • Listeria monocytogenes
  • Mage-b DNA vaccine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Mage-b vaccine delivered by recombinant Listeria monocytogenes is highly effective against breast cancer metastases. / Kim, S. H.; Castro, F.; Gonzalez, D.; Maciag, P. C.; Paterson, Y.; Gravekamp, Claudia.

In: British Journal of Cancer, Vol. 99, No. 5, 02.09.2008, p. 741-749.

Research output: Contribution to journalArticle

Kim, S. H. ; Castro, F. ; Gonzalez, D. ; Maciag, P. C. ; Paterson, Y. ; Gravekamp, Claudia. / Mage-b vaccine delivered by recombinant Listeria monocytogenes is highly effective against breast cancer metastases. In: British Journal of Cancer. 2008 ; Vol. 99, No. 5. pp. 741-749.
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