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
| Autor: | Amy Hobeika, Michael A. Morse, Herbert Kim Lyerly, Jennifer Zerfass, Zacharie Nickens, Ramila Philip, Julie Hafner, Peter Block, Gomathinayagam Sinnathamby, Angeles Alvarez Secord |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
Translational Studies T cell T-Lymphocytes Immunology Antigen presentation Epitopes T-Lymphocyte Gene Expression Breast Neoplasms ADAM17 Protein Major histocompatibility complex Lymphocyte Activation Epitope Granzymes Interferon-gamma Antigen Antigens Neoplasm Cell Line Tumor HLA-A2 Antigen medicine Immunology and Allergy Cytotoxic T cell Humans Antigen-presenting cell Ovarian Neoplasms Antigen Presentation biology Histocompatibility Antigens Class I Membrane Proteins Prostatic Neoplasms Peptide Fragments Gene Expression Regulation Neoplastic ADAM Proteins medicine.anatomical_structure Cancer cell biology.protein Leukocytes Mononuclear Female Immunotherapy T-Lymphocytes Cytotoxic |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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