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

Br J Cancer. 2008 Sep 2;99(5):741-9. doi: 10.1038/sj.bjc.6604526. Epub 2008 Aug 19.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • Base Sequence
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / genetics
  • Cancer Vaccines / therapeutic use
  • Cell Line, Tumor
  • DNA Primers
  • Female
  • Listeria monocytogenes / genetics*
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / immunology
  • Mammary Neoplasms, Experimental / pathology
  • Mammary Neoplasms, Experimental / therapy*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Metastasis / drug therapy*
  • Neoplasm Metastasis / immunology
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology*
  • Recombination, Genetic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Treatment Outcome

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • DNA Primers
  • Mageb1 protein, mouse
  • Mageb2 protein, mouse
  • Neoplasm Proteins