Nonredundant roles of antibody, cytokines, and perforin in the eradication of established Her-2/neu carcinomas

J Clin Invest. 2003 Apr;111(8):1161-70. doi: 10.1172/JCI17426.


Since the mechanisms by which specific immunity destroys Her-2/neu carcinoma cells are highly undetermined, these were assessed in BALB/c mice vaccinated with plasmids encoding extracellular and transmembrane domains of the protein product (p185(neu)) of the rat Her-2/neu oncogene shot into the skin by gene gun. Vaccinated mice rejected a lethal challenge of TUBO carcinoma cells expressing p185(neu). Depletion of CD4 T cells during immunization abolished the protection, while depletion of CD8 cells during the effector phase halved it, and depletion of polymorphonuclear granulocytes abolished all protection. By contrast, Ig mu-chain gene KO mice, as well as Fcgamma receptor I/III, beta-2 microglobulin, CD1, monocyte chemoattractant protein 1 (MCP1), IFN-gamma, and perforin gene KO mice were protected. Only mice with both IFN-gamma and perforin gene KOs were not protected. Although immunization also cured all BALB/c mice bearing established TUBO carcinomas, it did not cure any of the perforin KO or perforin and IFN-gamma KO mice. Few mice were cured that had knockouts of the gene for Ig mu-chain, Fcgamma receptor I/III, IFN-gamma, or beta-2 microglobulin. Moreover, vaccination cured half of the CD1 and the majority of the MCP1 KO mice. The eradication of established p185(neu) carcinomas involves distinct mechanisms, each endowed with a different curative potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neoplasm / physiology*
  • Biolistics
  • Cancer Vaccines / immunology*
  • Cytokines / physiology*
  • Female
  • Graft Rejection
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Neoplasm Transplantation
  • Neoplasms, Experimental / therapy*
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • Receptor, ErbB-2 / immunology*
  • Vaccination
  • Vaccines, DNA / immunology*


  • Antibodies, Neoplasm
  • Cancer Vaccines
  • Cytokines
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Vaccines, DNA
  • Perforin
  • Receptor, ErbB-2