Enhanced immunity by NeuEDhsp70 DNA vaccine Is needed to combat an aggressive spontaneous metastatic breast cancer

Mol Ther. 2005 Jun;11(6):941-9. doi: 10.1016/j.ymthe.2005.01.003.

Abstract

The rapid growth and ruthless metastasis of tumors demand effective broad immune responses. Dendritic cells (DCs) are critical in developing tumor vaccines. Recent investigations have been focused on modifying tumor antigens to target DCs to induce immune responses efficiently in vivo. In this study, human hsp70 was fused to the extracellular domain of rat Her2/Neu (NeuEDhsp70) for enhancing anti-tumor immunity in aggressive breast tumor models. NeuEDhsp70-conditioned DCs produced significant IL-12p40 and effectively presented NeuED antigens to T cells in vitro. NeuEDhsp70 DNA vaccine induced enhanced Neu-specific antibody and IFN-gamma-producing cellular immune responses in vivo. Although NeuEDhsp70 and NeuED DNA vaccines elicited comparable therapeutic anti-tumor immunity in an aggressive primary breast tumor model, NeuEDhsp70 DNA vaccine significantly increased survival and reduced metastasis in an aggressive spontaneous metastatic breast tumor model. Results from animal experiments with depletion of immune cells or with deficiency of CD40 molecules indicate that T cells and CD40 molecules are critical in the anti-tumor immunity induced by NeuEDhsp70 DNA vaccine. These observations suggest that NeuEDhsp70 DNA vaccine is a promising reagent to induce potent anti-tumor immunity to an aggressive spontaneous metastatic breast tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • Bone Marrow Neoplasms / prevention & control*
  • Bone Marrow Neoplasms / secondary
  • CD4-Positive T-Lymphocytes / immunology
  • CD40 Antigens / analysis
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / therapeutic use*
  • Dendritic Cells / immunology
  • Female
  • Interleukin-12 / analysis
  • Interleukin-12 Subunit p40
  • Mammary Neoplasms, Animal / drug therapy*
  • Mammary Neoplasms, Animal / immunology
  • Mammary Neoplasms, Animal / pathology
  • Mice
  • Protein Subunits / analysis
  • Rats
  • Receptor, ErbB-2 / immunology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology*
  • Vaccines, DNA / immunology
  • Vaccines, DNA / therapeutic use

Substances

  • Antigens, Neoplasm
  • CD40 Antigens
  • Cancer Vaccines
  • Interleukin-12 Subunit p40
  • NeuEDhsp70 fusion protein, recombinant
  • Protein Subunits
  • Recombinant Fusion Proteins
  • Vaccines, DNA
  • Interleukin-12
  • Receptor, ErbB-2