Hsp110 over-expression increases the immunogenicity of the murine CT26 colon tumor

Cancer Immunol Immunother. 2002 Aug;51(6):311-9. doi: 10.1007/s00262-002-0287-1. Epub 2002 Jun 13.


Several studies have suggested a positive correlation between heat shock protein (hsp) expression and tumor immunogenicity. Independently, many studies have shown that hsp purified from tumors can be used as a tumor-specific vaccine. In this study, we have explored the connection between hsp expression and anti-tumor immunity by transducing murine CT26 colon carcinoma cells with the cDNA of a major hsp, i.e. hsp110. We have shown that over-expression of hsp110 has no effect on CT26 tumor cell growth in vitro, and does not inhibit their anchorage-independent growth capacity. However, in situ, hsp110 over-expressing CT26 tumor (CT26-hsp110) grew at a significantly reduced rate as compared to the wild-type CT26 tumor in immunocompetent mice. Moreover, immunization of mice with inactivated CT26-hsp110 cells significantly inhibited the growth of wild-type CT26 tumor. This immunity was associated with an increased frequency of tumor-specific T cells after vaccination. An in vivo antibody depletion assay demonstrated that inactivated CT26-hsp110 cells elicited anti-tumor responses involving CD8(+) T cells and natural killer (NK) cells, but not CD4(+) T cells. Lastly, the effect of the addition of granulocyte-macrophage colony stimulating factor (GM-CSF) to these vaccine formulations was determined. Mice immunized with irradiated CT26-hsp110 cells combined with GM-CSF-producing bystander cells revealed a complete inhibition of CT26 tumor growth, indicating a synergy between inactivated CT26-hsp110 vaccine activity and GM-CSF. These observations demonstrate that manipulation of hsp110 expression in tumors, specifically when combined with GM-CSF, represents a potentially powerful approach to cancer vaccine formulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen Presentation
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / immunology*
  • Carcinoma / immunology*
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Coculture Techniques
  • Colonic Neoplasms / immunology*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Cytotoxicity, Immunologic
  • DNA, Complementary / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • HSP110 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins / biosynthesis
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / physiology*
  • Killer Cells, Natural / immunology
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Neoplasm Transplantation / immunology
  • Recombinant Fusion Proteins / physiology
  • Specific Pathogen-Free Organisms
  • Transfection
  • Tumor Cells, Cultured / immunology
  • Tumor Cells, Cultured / radiation effects
  • Vaccination


  • Cancer Vaccines
  • DNA, Complementary
  • HSP110 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • Hsp105 protein, mouse
  • Neoplasm Proteins
  • Recombinant Fusion Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor