title: MMP11: a novel target antigen for cancer immunotherapy.
abstract: OBJECTIVE
  Matrix metalloproteinases (MMP) are zinc-dependent endopeptidases that mediate numerous physiologic and pathologic processes, including matrix degradation, tissue remodeling, inflammation, and tumor metastasis. To develop a vaccine targeting stromal antigens expressed by cancer-associated fibroblasts, we focused on MMP11 (or stromelysin 3). MMP11 expression correlates with aggressive profile and invasiveness of different types of carcinoma.
  
  
  METHODS
  To show the efficacy of a vaccine targeting MMP11, we constructed a series of plasmid DNA vectors expressing murine MMP11. Mice were vaccinated by i.m. injection followed by in vivo DNA electroporation. A chemically induced, MMP11-overexpressing colon cancer model was established and characterized. Antibody and T-cell responses were determined, and immunoreactive epitopes were characterized. To analyze the possible use of MMP11 as tumor-associated antigen in cancer patients, HLA-A2.1 transgenic mice (HHD) were used to identify reactive epitopes as tools to assess immunogenicity in humans.
  
  
  RESULTS
  Using microarray, we confirmed the overexpression of MMP11 mRNA in a large panel of human tumor samples. MMP11 vaccine induced cell mediated and antibody immune response and exerted significant antitumoral protection in mice with colon cancer in prophylactic and therapeutic settings. HHD transgenic mice were vaccinated with a plasmid encoding human MMP11, and a HLA-A2.1--restricted epitope (hMMP(237)) was identified. hMMP(237) was shown to be immunogenic in human peripheral blood mononuclear cells (PBMC) by in vitro priming.
  
  
  CONCLUSIONS
  Our study describes the identification of MMP11 as a novel broadly expressed tumor associated antigen as target candidate for cancer immunotherapy.
authors.affiliation: Istituto di Ricerca di Biologia Molecolare-Merck Research Laboratories, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Peruzzi
authors.forename: Federica
authors.initials: F
authors.lastname: Mori
authors.forename: Antonella
authors.initials: A
authors.lastname: Conforti
authors.forename: Domenico
authors.initials: D
authors.lastname: Lazzaro
authors.forename: Emanuele
authors.initials: E
authors.lastname: De Rinaldis
authors.forename: Gennaro
authors.initials: G
authors.lastname: Ciliberto
authors.forename: Nicola
authors.initials: N
authors.lastname: La Monica
authors.forename: Luigi
authors.initials: L
authors.lastname: Aurisicchio
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D000939:Epitopes / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D053507:Matrix Metalloproteinase 11 / Q000276:immunology*; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D014162:Transfection
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes; D015789:HLA-A2 Antigen; D061965:Matrix Metalloproteinase Inhibitors; D053507:Matrix Metalloproteinase 11