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A Single-Agent Dual-Specificity Targeting of FOLR1 and DR5 as an Effective Strategy for Ovarian Cancer.
Shivange, Gururaj; Urbanek, Karol; Przanowski, Piotr; Perry, Justin S A; Jones, James; Haggart, Robert; Kostka, Christina; Patki, Tejal; Stelow, Edward; Petrova, Yuliya; Llaneza, Danielle; Mayo, Marty; Ravichandran, Kodi S; Landen, Charles N; Bhatnagar, Sanchita; Tushir-Singh, Jogender.
Afiliação
  • Shivange G; Laboratory of Novel Biologics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; UVA Cancer Center, University of Virginia School of Medicine, Charlo
  • Urbanek K; Laboratory of Novel Biologics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; UVA Cancer Center, University of Virginia School of Medicine, Charlo
  • Przanowski P; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; UVA Cancer Center, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
  • Perry JSA; Center for Cell Clearance and Department of Microbiology, Immunology, Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
  • Jones J; Laboratory of Novel Biologics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; Undergraduate Research Program, University of Virginia School of Med
  • Haggart R; Laboratory of Novel Biologics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; Undergraduate Research Program, University of Virginia School of Med
  • Kostka C; Laboratory of Novel Biologics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; Undergraduate Research Program, University of Virginia School of Med
  • Patki T; Laboratory of Novel Biologics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; Undergraduate Research Program, University of Virginia School of Med
  • Stelow E; Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
  • Petrova Y; Department of Obstetrics and Gynecology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; UVA Cancer Center, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
  • Llaneza D; Department of Obstetrics and Gynecology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; UVA Cancer Center, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
  • Mayo M; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
  • Ravichandran KS; Center for Cell Clearance and Department of Microbiology, Immunology, Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
  • Landen CN; Department of Obstetrics and Gynecology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; UVA Cancer Center, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
  • Bhatnagar S; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; UVA Cancer Center, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
  • Tushir-Singh J; Laboratory of Novel Biologics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; UVA Cancer Center, University of Virginia School of Medicine, Charlo
Cancer Cell ; 34(2): 331-345.e11, 2018 08 13.
Article em En | MEDLINE | ID: mdl-30107179
ABSTRACT
Therapeutic antibodies targeting ovarian cancer (OvCa)-enriched receptors have largely been disappointing due to limited tumor-specific antibody-dependent cellular cytotoxicity. Here we report a symbiotic approach that is highly selective and superior compared with investigational clinical antibodies. This bispecific-anchored cytotoxicity activator antibody is rationally designed to instigate "cis" and "trans" cytotoxicity by combining specificities against folate receptor alpha-1 (FOLR1) and death receptor 5 (DR5). Whereas the in vivo agonist DR5 signaling requires FcγRIIB interaction, the FOLR1 anchor functions as a primary clustering point to retain and maintain a high level of tumor-specific apoptosis. The presented proof of concept study strategically makes use of a tumor cell-enriched anchor receptor for agonist death receptor targeting to potentially generate a clinically viable strategy for OvCa.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Anticorpos Biespecíficos / Receptores do Ligante Indutor de Apoptose Relacionado a TNF / Receptor 1 de Folato Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Anticorpos Biespecíficos / Receptores do Ligante Indutor de Apoptose Relacionado a TNF / Receptor 1 de Folato Idioma: En Ano de publicação: 2018 Tipo de documento: Article