{"corpus_id":19365513,"paper_sha":"69cceb2a13d9fe9abfeee1fecb7637f795123d1c","doi":"10.1593/TLO.10211","arxiv_id":null,"pmid":21286376,"pmcid":"PMC3026407","mag_id":2001835704,"dblp_id":null,"acl_id":null,"title":"Isolation of Fully Human Antagonistic RON Antibodies Showing Efficient Block of Downstream Signaling and Cell Migration.","year":2011,"publication_date":"2011-02-01","venue":"Translational Oncology","journal":{"name":"Translational oncology","pages":"\n          38-46\n        ","volume":"4 1"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":45,"citation_count":14,"influential_citation_count":0,"is_open_access":false,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":null,"chemicals":null,"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":null,"s2_open_access_landing_url":null,"s2_open_access_license":null,"s2_open_access_status":null,"pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"RON belongs to the c-MET family of receptor tyrosine kinases. As its well-known family member MET, RON and its ligand macrophage-stimulating protein have been implicated in the progression and metastasis of tumors and have been shown to be overexpressed in cancer. We generated and tested a large number of human monoclonal antibodies (mAbs) against human RON. Our screening yielded three high-affinity antibodies that efficiently block ligand-dependent intracellular AKT and MAPK signaling. This effect correlates with the strong reduction of ligand-activated migration of T47D breast cancer cell line. By cross-competition experiments, we showed that the antagonistic antibodies fall into three distinct epitope regions of the RON extracellular Sema domain. Notably, no inhibition of tumor growth was observed in different epithelial tumor xenografts in nude mice with any of the antibodies. These results suggest that distinct properties beside ligand antagonism are required for anti-RON mAbs to exert antitumor effects in vivo.","claims":[{"public_id":"cl_068fe7933000a0b32eba6bb870a91c07","status":"active","text":"Ligand antagonism alone is insufficient for anti-RON monoclonal antibodies to produce antitumor effects in vivo.","confidence":0.9,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_068fe7933000a0b32eba6bb870a91c07"},{"public_id":"cl_10ea94fb839eec3d088d975b6fe470b4","status":"active","text":"No inhibition of tumor growth was observed in epithelial tumor xenografts in nude mice with any of the antibodies.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_10ea94fb839eec3d088d975b6fe470b4"},{"public_id":"cl_cf4e9b16e563d9fd76864637f498d4e9","status":"active","text":"The antagonistic antibodies map to three distinct epitope regions within the RON extracellular Sema domain.","confidence":0.93,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_cf4e9b16e563d9fd76864637f498d4e9"},{"public_id":"cl_e207cc1ea0db84abe98b9fe554a94579","status":"active","text":"The signaling blockade is associated with a strong reduction of ligand-activated migration in T47D breast cancer cells.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_e207cc1ea0db84abe98b9fe554a94579"},{"public_id":"cl_bfcba473ec479e7b6129d9b99a050d99","status":"active","text":"Three high-affinity fully human anti-RON antibodies were identified that efficiently block ligand-dependent AKT and MAPK signaling.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_bfcba473ec479e7b6129d9b99a050d99"}],"concepts":[{"public_id":"co_181a2dc51b7fae21ea9f2458b6aa9a68","status":"active","name":"nude mice","description":"Immunodeficient mice used as hosts for xenograft experiments.","types":["animal model"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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