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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.

Publication ,  Journal Article
Sinnathamby, G; Zerfass, J; Hafner, J; Block, P; Nickens, Z; Hobeika, A; Secord, AA; Lyerly, HK; Morse, MA; Philip, R
Published in: Clin Exp Immunol
March 2011

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.

Duke Scholars

Published In

Clin Exp Immunol

DOI

EISSN

1365-2249

Publication Date

March 2011

Volume

163

Issue

3

Start / End Page

324 / 332

Location

England

Related Subject Headings

  • T-Lymphocytes, Cytotoxic
  • T-Lymphocytes
  • Prostatic Neoplasms
  • Peptide Fragments
  • Ovarian Neoplasms
  • Membrane Proteins
  • Male
  • Lymphocyte Activation
  • Leukocytes, Mononuclear
  • Interferon-gamma
 

Citation

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Sinnathamby, G., Zerfass, J., Hafner, J., Block, P., Nickens, Z., Hobeika, A., … Philip, R. (2011). 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, 163(3), 324–332. https://doi.org/10.1111/j.1365-2249.2010.04298.x
Sinnathamby, G., J. Zerfass, J. Hafner, P. Block, Z. Nickens, A. Hobeika, A. A. Secord, H. K. Lyerly, M. A. Morse, and R. Philip. “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 163, no. 3 (March 2011): 324–32. https://doi.org/10.1111/j.1365-2249.2010.04298.x.
Sinnathamby G, Zerfass J, Hafner J, Block P, Nickens Z, Hobeika A, Secord AA, Lyerly HK, Morse MA, Philip R. 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):324–332.
Journal cover image

Published In

Clin Exp Immunol

DOI

EISSN

1365-2249

Publication Date

March 2011

Volume

163

Issue

3

Start / End Page

324 / 332

Location

England

Related Subject Headings

  • T-Lymphocytes, Cytotoxic
  • T-Lymphocytes
  • Prostatic Neoplasms
  • Peptide Fragments
  • Ovarian Neoplasms
  • Membrane Proteins
  • Male
  • Lymphocyte Activation
  • Leukocytes, Mononuclear
  • Interferon-gamma