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Yuan Qing-an , Simmons Heidi H , Robinson Matthew K , Russeva Maria , Marasco Wayne A , Adams Gregory P
Development of engineered antibodies specific for the Muellerian inhibiting substance type II receptor: a promising candidate for targeted therapy of ovarian cancer
Molecular Cancer Therapeutics. 2006 ;5(8) :2096-2105
PMID: AN 2006:842432
AbstractThe Muellerian inhibiting substance type II receptor (MISIIR) is involved in Muellerian duct regression as part of the development of the male reproductive system. In adult females, MISIIR is present on ovarian surface epithelium and is frequently expressed on human epithelial ovarian cancer cells. Muellerian inhibiting substance has been found to be capable of inhibiting the growth of primary human ovarian cancer cells derived from ascites and ovarian cancer cell lines. This suggested to us that MISIIR could be an attractive target for antibody-based tumor targeting and growth inhibition strategies. Here, we describe the prodn. of recombinant human MISIIR extracellular domain-human Ig Fc domain fusion proteins and their use as targets for the selection of MISIIR-specific human single-chain variable fragments (scFv) mols. from a human nonimmune scFv phage display library. The binding kinetics of the resulting anti-MISIIR scFv clones were characterized and two were employed as the basis for the construction of bivalent scFv:Fc antibody-based mols. Both bound specifically to human ovarian carcinoma cells in flow cytometry assays and cross-reacted with mouse MISIIR. These results indicate that antibody-based constructs may provide a highly specific means of targeting MISIIR on human ovarian carcinoma cells for the purpose of diagnosing and treating this disease. [on SciFinder (R)]
NotesCAN 145:333772 15-3 Immunochemistry Department of Medical Oncology Philadelphia, Pennsylvania,Fox Chase Cancer Center,Phildadelphia,PA,USA. Journal 1535-7163 written in English.