title: Matrilysin (MMP-7) is a novel broadly expressed tumor antigen recognized by antigen-specific T cells.
abstract: OBJECTIVE
  A prerequisite for the development of vaccination strategies is the identification and characterization of relevant tumor-associated antigen. Using microarray and reverse transcription-PCR analysis, we found matrix metalloproteinase (MMP)-7 to be extensively up-regulated in renal cell carcinomas and expressed in a broad variety of malignant cells. MMP-7 can promote cancer invasion and angiogenesis by proteolytic cleavage of extracellular matrix and basement membrane proteins, thus making it a promising target in the context of immunotherapies.
  
  
  METHODS
  To analyze the possible use of MMP-7 as a tumor-associated antigen, specific CTLs were induced using monocyte-derived dendritic cells electroporated with MMP-7-mRNA. In addition, to better characterize the fine specificity of these CTLs, MMP-7 MHC class I ligands were isolated and characterized in renal cell carcinoma tissue, which overexpressed MMP-7, by mass spectrometry-based peptide sequencing. Using this approach, we identified a novel HLA-A3-binding antigenic MMP-7 peptide. CTLs generated from healthy donors by in vitro priming with dendritic cells, pulsed with the novel peptide, were used as effectors in (51)Cr-release assays.
  
  
  RESULTS
  The induced CTLs elicited an antigen-specific and HLA-restricted cytolytic activity against tumor cells endogenously expressing the MMP-7 protein. Furthermore, we were able to induce MMP-7-specific CTLs using peripheral blood mononuclear cells from a patient with acute lymphoblastic leukemia capable of recognizing the autologous leukemic blasts while sparing nonmalignant cells.
  
  
  CONCLUSIONS
  Our study describes the identification of a novel broadly expressed T-cell epitope derived from the MMP-7 protein that represents an interesting candidate to be applied in immunotherapies of human malignancies targeting both tumor cells and neovascularization.
authors.affiliation: Department Of Oncology, Hematology, Immunology, Rheumatology And Pulmology, University Of Tübingen, Tübingen, Germany.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Frank
authors.initials: F
authors.lastname: Grünebach
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Schmidt
authors.forename: Annkristin
authors.initials: A
authors.lastname: Heine
authors.forename: Maik
authors.initials: M
authors.lastname: Häntschel
authors.forename: Stefan
authors.initials: S
authors.lastname: Stevanovic
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.forename: Peter
authors.initials: P
authors.lastname: Brossart