Document Detail


A novel bispecific single-chain antibody for ADAM17 and CD3 induces T-cell mediated lysis of prostate cancer cells.
MedLine Citation:
PMID:  22509934     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
A disintegrin and metalloproteinase 17 (ADAM17) is a membrane-bound protease that cleaves various cell surface proteins including cytokines and cytokine receptors. Recently it was shown that ADAM17 is highly expressed on the surface of many cancer cells whereas normal cells express low levels of ADAM17, implying ADAM17 as a potential immunotherapeutic target. We have generated a monoclonal antibody against human ADAM17, which recognized the membrane proximal cysteine-rich extension of the ADAM17 protein. Unlike normal cells, tumor cell lines such as a prostate cancer cell line, pancreatic cancer cell lines, a breast cancer cell line and a non-small lung cancer cell line expressed ADAM17 on the cell surface. Using the sequence of the antibody we generated an ADAM17-specific single-chain antibody (scFv) and fused this to a CD3-specific scFv to generate a bispecific T-cell engager antibody (A300E-BiTE). Specificity was demonstrated on cells in which ADAM17 was knocked down with a specific shRNA. A300E-BiTE recognized ADAM17 and CD3 on the cell surface of tumor cells and T-cells, respectively. In the presence of primary human peripheral blood mononuclear cells or human T-cells addition of A300E-BiTE led to ADAM17 specific killing of prostate tumor cells indicating a novel strategy for the treatment of cancer.
Authors:
Kosuke Yamamoto; Ahmad Trad; Anja Baumgart; Linda Hüske; Inken Lorenzen; Athena Chalaris; Joachim Grötzinger; Tobias Dechow; Jürgen Scheller; Stefan Rose-John
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-17
Journal Detail:
Title:  The Biochemical journal     Volume:  -     ISSN:  1470-8728     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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