Development of a live and highly attenuated Listeria monocytogenes-based vaccine for the treatment of Her2/neu-overexpressing cancers in human

Cancer Gene Ther. 2011 Jan;18(1):53-62. doi: 10.1038/cgt.2010.48. Epub 2010 Aug 20.


A chimeric human Her2/neu gene (ChHer2) harboring most of the known major histocompatibility complex class I epitopes of the HER2/neu oncogene was expressed as a fusion protein to a non-hemolytic fragment of listeriolysin O (LLO), by the highly attenuated Listeria vector LmddA, which lacks antibiotic selection markers and the ability to spread from cell-to-cell. This construct (ADXS31-164) was tested for immunogenicity and anti-tumor effects in mice. Despite being highly attenuated, ADXS31-164 proved to be efficacious in breaking immune tolerance toward the HER2/neu self-antigen. ADXS31-164 elicited strong T-cell immune responses in experimental animals. In tumors, ADXS31-164 caused a reduction in regulatory T cells (Treg) accompanied by an increase in the CD8(+)/Treg ratio. Comparison of this vaccine with the conventional antibiotic resistant Listeria vector (Lm-LLO-ChHer2) shows that ADXS31-164 is more efficacious in delaying tumor growth in Her2/neu transgenic animals. Because of its well-defined attenuation mechanism and independence from antibiotic selection markers, ADXS31-164 is potentially more suitable for human use. These results support the future clinical development of this vaccine for the treatment of HER2/neu-overexpressing malignancies, such as breast, colorectal and pancreatic cancers.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Breast Neoplasms / prevention & control
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / metabolism*
  • Cell Line, Tumor
  • Female
  • Humans
  • Immunotherapy / methods
  • Listeria monocytogenes*
  • Mammary Neoplasms, Animal / immunology
  • Mammary Neoplasms, Animal / prevention & control
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Rats
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*
  • Vaccines, Attenuated / genetics
  • Vaccines, Attenuated / immunology*
  • Vaccines, Attenuated / metabolism*


  • Cancer Vaccines
  • Vaccines, Attenuated
  • Receptor, ErbB-2