MMP11: A novel target antigen for cancer immunotherapy

Daniela Peruzzi, Federica Mori, Antonella Conforti, Domenico Lazzaro, Emanuele De Rinaldis, Gennaro Ciliberto, Nicola La Monica, Luigi Aurisicchio

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Abstract

Purpose: 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. Experimental Design: 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 (hMMP237) was identified. hMMP237 was shown to be immunogenic in human peripheral blood mononuclear cells (PBMC) by in vitro priming. Conclusion: Our study describes the identification of MMP11 as a novel broadly expressed tumor associated antigen as target candidate for cancer immunotherapy.

Original languageEnglish
Pages (from-to)4104-4113
Number of pages10
JournalClinical Cancer Research
Volume15
Issue number12
DOIs
Publication statusPublished - Jun 15 2009

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Peruzzi, D., Mori, F., Conforti, A., Lazzaro, D., De Rinaldis, E., Ciliberto, G., La Monica, N., & Aurisicchio, L. (2009). MMP11: A novel target antigen for cancer immunotherapy. Clinical Cancer Research, 15(12), 4104-4113. https://doi.org/10.1158/1078-0432.CCR-08-3226