http://purl.uniprot.org/citations/16489096 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/16489096 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/16489096 | http://www.w3.org/2000/01/rdf-schema#comment | "PurposeAdvanced melanoma is a highly drug-refractory neoplasm representing a significant unmet medical need. We sought to identify melanoma-associated cell surface molecules and to develop as well as preclinically test immunotherapeutic reagents designed to exploit such targets.Experimental design and resultsBy transcript profiling, we identified glycoprotein NMB (GPNMB) as a gene that is expressed by most metastatic melanoma samples examined. GPNMB is predicted to be a transmembrane protein, thus making it a potential immunotherapeutic target in the treatment of this disease. A fully human monoclonal antibody, designated CR011, was generated to the extracellular domain of GPNMB and characterized for growth-inhibitory activity against melanoma. The CR011 monoclonal antibody showed surface staining of most melanoma cell lines by flow cytometry and reacted with a majority of metastatic melanoma specimens by immunohistochemistry. CR011 alone did not inhibit the growth of melanoma cells. However, when linked to the cytotoxic agent monomethylauristatin E (MMAE) to generate the CR011-vcMMAE antibody-drug conjugate, this reagent now potently and specifically inhibited the growth of GPNMB-positive melanoma cells in vitro. Ectopic overexpression and small interfering RNA transfection studies showed that GPNMB expression is both necessary and sufficient for sensitivity to low concentrations of CR011-vcMMAE. In a melanoma xenograft model, CR011-vcMMAE induced significant dose-proportional antitumor effects, including complete regressions, at doses as low as 1.25 mg/kg.ConclusionThese preclinical results support the continued evaluation of CR011-vcMMAE for the treatment of melanoma."xsd:string |
http://purl.uniprot.org/citations/16489096 | http://purl.org/dc/terms/identifier | "doi:10.1158/1078-0432.ccr-05-2018"xsd:string |
http://purl.uniprot.org/citations/16489096 | http://purl.org/dc/terms/identifier | "doi:10.1158/1078-0432.ccr-05-2018"xsd:string |
http://purl.uniprot.org/citations/16489096 | http://purl.uniprot.org/core/author | "Gallo M."xsd:string |
http://purl.uniprot.org/citations/16489096 | http://purl.uniprot.org/core/author | "Gallo M."xsd:string |
http://purl.uniprot.org/citations/16489096 | http://purl.uniprot.org/core/author | "Khramtsov N.V."xsd:string |
http://purl.uniprot.org/citations/16489096 | http://purl.uniprot.org/core/author | "Khramtsov N.V."xsd:string |
http://purl.uniprot.org/citations/16489096 | http://purl.uniprot.org/core/author | "Herrmann J."xsd:string |
http://purl.uniprot.org/citations/16489096 | http://purl.uniprot.org/core/author | "Herrmann J."xsd:string |
http://purl.uniprot.org/citations/16489096 | http://purl.uniprot.org/core/author | "Hackett C.S."xsd:string |
http://purl.uniprot.org/citations/16489096 | http://purl.uniprot.org/core/author | "Hackett C.S."xsd:string |
http://purl.uniprot.org/citations/16489096 | http://purl.uniprot.org/core/author | "Lichenstein H.S."xsd:string |
http://purl.uniprot.org/citations/16489096 | http://purl.uniprot.org/core/author | "Lichenstein H.S."xsd:string |
http://purl.uniprot.org/citations/16489096 | http://purl.uniprot.org/core/author | "Rastelli L."xsd:string |
http://purl.uniprot.org/citations/16489096 | http://purl.uniprot.org/core/author | "Rastelli L."xsd:string |
http://purl.uniprot.org/citations/16489096 | http://purl.uniprot.org/core/author | "Senter P.D."xsd:string |
http://purl.uniprot.org/citations/16489096 | http://purl.uniprot.org/core/author | "Senter P.D."xsd:string |
http://purl.uniprot.org/citations/16489096 | http://purl.uniprot.org/core/author | "Boldog F.L."xsd:string |
http://purl.uniprot.org/citations/16489096 | http://purl.uniprot.org/core/author | "Boldog F.L."xsd:string |
http://purl.uniprot.org/citations/16489096 | http://purl.uniprot.org/core/author | "Jeffers M."xsd:string |
http://purl.uniprot.org/citations/16489096 | http://purl.uniprot.org/core/author | "Jeffers M."xsd:string |
http://purl.uniprot.org/citations/16489096 | http://purl.uniprot.org/core/author | "LaRochelle W.J."xsd:string |
http://purl.uniprot.org/citations/16489096 | http://purl.uniprot.org/core/author | "LaRochelle W.J."xsd:string |