ADAM metallopeptidase domain 17 (ADAM17) is naturally processed through major histocompatibility complex (MHC) class I molecules and is a potential immunotherapeutic target in breast, ovarian and prostate cancers

Clin Exp Immunol. 2011 Mar;163(3):324-32. doi: 10.1111/j.1365-2249.2010.04298.x. Epub 2010 Dec 22.


Selection of suitable antigens is critical for the development of cancer vaccines. Most desirable are over-expressed cell surface proteins that may serve as targets for both antibodies and T cells, thus maximizing a concerted immune response. Towards this goal, we characterized the relevance of tumour necrosis factor-α-converting enzyme (ADAM17) for such targeted therapeutics. ADAM17 is one of the several metalloproteinases that play a key role in epidermal growth factor receptor (EGFR) signalling and has recently emerged as a new therapeutic target in several tumour types. In the present study, we analysed the expression profile of ADAM17 in a variety of normal and cancer cells of human origin and found that this protein is over-expressed on the surface of several types of cancer cells compared to the normal counterparts. Furthermore, we analysed the presentation of a human leucocyte antigen (HLA)-A2-restricted epitope from ADAM17 protein to specific T cells established from normal donors as well as ovarian cancer patients. Our analysis revealed that the HLA-A2-restricted epitope is processed efficiently and presented by various cancer cells and not by normal cells. Tumour-specific T cell activation results in the secretion of both interferon-γ and granzyme B that can be blocked by HLA-A2 specific antibodies. Collectively, our data present evidence that ADAM17 can be a potential target antigen to devise novel immunotherapeutic strategies against ovarian, breast and prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / genetics
  • ADAM Proteins / immunology*
  • ADAM Proteins / metabolism
  • ADAM17 Protein
  • Antigen Presentation / immunology
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / therapy
  • Cell Line, Tumor
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Gene Expression / genetics
  • Gene Expression Regulation, Neoplastic / physiology
  • Granzymes / metabolism
  • HLA-A2 Antigen / immunology
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Immunotherapy*
  • Interferon-gamma / metabolism
  • Leukocytes, Mononuclear / immunology
  • Lymphocyte Activation / immunology
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism
  • Ovarian Neoplasms / immunology*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / therapy
  • Peptide Fragments / immunology
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / therapy
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism


  • Antigens, Neoplasm
  • Epitopes, T-Lymphocyte
  • HLA-A2 Antigen
  • Histocompatibility Antigens Class I
  • Membrane Proteins
  • Peptide Fragments
  • Interferon-gamma
  • Granzymes
  • ADAM Proteins
  • ADAM17 Protein
  • ADAM17 protein, human