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.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Sinnathamby, G; Zerfass, J; Hafner, J; Block, P; Nickens, Z; Hobeika, A; Secord, AA; Lyerly, HK; Morse, MA; Philip, R

Published Date

  • March 2011

Published In

Volume / Issue

  • 163 / 3

Start / End Page

  • 324 - 332

PubMed ID

  • 21175594

Pubmed Central ID

  • PMC3048615

Electronic International Standard Serial Number (EISSN)

  • 1365-2249

Digital Object Identifier (DOI)

  • 10.1111/j.1365-2249.2010.04298.x


  • eng

Conference Location

  • England