A Mage3/Heat Shock Protein70 DNA vaccine induces both innate and adaptive immune responses for the antitumor activity.
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.
Wang
Lifeng
L
Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, United States.
Rollins
Lisa
L
Gu
Qinlong
Q
Chen
Si-Yi
SY
Huang
Xue F
XF
D056704:Adaptive Immunity / Q000187:drug effects; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005822:Genetic Vectors; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate / Q000187:drug effects; D047468:Immunoprecipitation; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018840:HSP70 Heat-Shock Proteins; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D019444:Vaccines, DNA