title: A Mage3/Heat Shock Protein70 DNA vaccine induces both innate and adaptive immune responses for the antitumor activity.
abstract: 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.
authors.affiliation: Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, United States.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Wang
authors.forename: Lisa
authors.initials: L
authors.lastname: Rollins
authors.forename: Qinlong
authors.initials: Q
authors.lastname: Gu
authors.forename: Si-Yi
authors.initials: SY
authors.lastname: Chen
authors.forename: Xue F
authors.initials: XF
authors.lastname: Huang
mesh_terms: 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*
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018840:HSP70 Heat-Shock Proteins; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; D019444:Vaccines, DNA