A Mage3/Heat Shock Protein70 DNA vaccine induces both innate and adaptive immune responses for the antitumor activity

Vaccine. 2009 Dec 11;28(2):561-70. doi: 10.1016/j.vaccine.2009.09.119. Epub 2009 Oct 14.


Heat shock proteins (HSPs) are highly effective and versatile molecules in promoting antitumor immune responses. We tested whether a HSP-based DNA vaccine can induce effective immune response against Mage3, a cancer testis (CT) antigen frequently expressed in many human tumors, thereby controlling the Mage3-expressing tumor. The vaccine was constructed by linking human inducible HSP70 to the C-terminus of a modified Mage3 gene (sMage3) that was attached at its N-terminus with the signal leader sequence of the human RANTES for releasing the expressed fusion protein from the transduced cells. Intramuscular injection of sMage3Hsp DNA induced CD4(+)/CD8(+) T cell and antibody responses. Vaccination with sMage3Hsp DNA was more effective in inhibiting Mage3-expressing TC-1 tumors. When we dissected the antitumor activity of CD4(+) and CD8(+) T cells by immunizing CD4(+) and CD8(+) knockout mice with sMage3Hsp DNA, we found that both CD8(+) T and CD4(+) T cells played a role in control of inoculated tumor, but did not constitute the whole of immune protection in the prophylactic immunization. Instead, depletion of natural killer (NK) cells led to a major loss of antitumor activity in the immunized mice. These results indicate that the HSP-based Mage3 DNA vaccine can more effectively inhibit tumor growth by inducing both the innate immune responses and Mage3-specific adaptive immune responses via the Hsp-associated adjuvant function.

Publication types

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

MeSH terms

  • Adaptive Immunity / drug effects
  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / pharmacology
  • Cancer Vaccines / therapeutic use*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genetic Vectors
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / immunology*
  • Immunity, Innate / drug effects
  • Immunoprecipitation
  • Mice
  • Mice, Knockout
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology*
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*
  • Vaccines, DNA / pharmacology
  • Vaccines, DNA / therapeutic use*


  • Antigens, Neoplasm
  • Cancer Vaccines
  • HSP70 Heat-Shock Proteins
  • MAGEA3 protein, human
  • Neoplasm Proteins
  • Vaccines, DNA