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Antagonistic human FcγRIIB (CD32B) antibodies have anti-tumor activity and overcome resistance to antibody therapy in vivo.
Roghanian, Ali; Teige, Ingrid; Mårtensson, Linda; Cox, Kerry L; Kovacek, Mathilda; Ljungars, Anne; Mattson, Jenny; Sundberg, Annika; Vaughan, Andrew T; Shah, Vallari; Smyth, Neil R; Sheth, Bhavwanti; Chan, H T Claude; Li, Zhan-Chun; Williams, Emily L; Manfredi, Giusi; Oldham, Robert J; Mockridge, C Ian; James, Sonya A; Dahal, Lekh N; Hussain, Khiyam; Nilsson, Björn; Verbeek, J Sjef; Juliusson, Gunnar; Hansson, Markus; Jerkeman, Mats; Johnson, Peter W M; Davies, Andrew; Beers, Stephen A; Glennie, Martin J; Frendéus, Björn; Cragg, Mark S.
Afiliación
  • Roghanian A; Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
  • Teige I; BioInvent International AB, Sölvegatan 41, 22370 Lund, Sweden.
  • Mårtensson L; BioInvent International AB, Sölvegatan 41, 22370 Lund, Sweden.
  • Cox KL; Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
  • Kovacek M; BioInvent International AB, Sölvegatan 41, 22370 Lund, Sweden.
  • Ljungars A; BioInvent International AB, Sölvegatan 41, 22370 Lund, Sweden.
  • Mattson J; BioInvent International AB, Sölvegatan 41, 22370 Lund, Sweden.
  • Sundberg A; BioInvent International AB, Sölvegatan 41, 22370 Lund, Sweden.
  • Vaughan AT; Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
  • Shah V; Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
  • Smyth NR; Centre for Biological Sciences, University of Southampton, Southampton SO16 6YD, UK.
  • Sheth B; Centre for Biological Sciences, University of Southampton, Southampton SO16 6YD, UK.
  • Chan HT; Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
  • Li ZC; BioInvent International AB, Sölvegatan 41, 22370 Lund, Sweden.
  • Williams EL; Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
  • Manfredi G; Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
  • Oldham RJ; Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
  • Mockridge CI; Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
  • James SA; Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
  • Dahal LN; Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
  • Hussain K; Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
  • Nilsson B; Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, 221 85 Lund, Sweden.
  • Verbeek JS; Department of Human Genetics, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, the Netherlands.
  • Juliusson G; Skåne University Hospital, Lund University, 221 84 Lund, Sweden.
  • Hansson M; Skåne University Hospital, Lund University, 221 84 Lund, Sweden.
  • Jerkeman M; Skåne University Hospital, Lund University, 221 84 Lund, Sweden.
  • Johnson PW; Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
  • Davies A; Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
  • Beers SA; Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
  • Glennie MJ; Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
  • Frendéus B; Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK; BioInvent International AB, Sölvegatan 41, 22370 Lund, Sweden.
  • Cragg MS; Antibody & Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK. Electronic address: msc@soton.ac.uk.
Cancer Cell ; 27(4): 473-88, 2015 Apr 13.
Article en En | MEDLINE | ID: mdl-25873171
Therapeutic antibodies have transformed cancer therapy, unlocking mechanisms of action by engaging the immune system. Unfortunately, cures rarely occur and patients display intrinsic or acquired resistance. Here, we demonstrate the therapeutic potential of targeting human (h) FcγRIIB (CD32B), a receptor implicated in immune cell desensitization and tumor cell resistance. FcγRIIB-blocking antibodies prevented internalization of the CD20-specific antibody rituximab, thereby maximizing cell surface accessibility and immune effector cell mediated antitumor activity. In hFcγRIIB-transgenic (Tg) mice, FcγRIIB-blocking antibodies effectively deleted target cells in combination with rituximab, and other therapeutic antibodies, from resistance-prone stromal compartments. Similar efficacy was seen in primary human tumor xenografts, including with cells from patients with relapsed/refractory disease. These data support the further development of hFcγRIIB antibodies for clinical assessment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de IgG / Anticuerpos Monoclonales de Origen Murino / Anticuerpos Monoclonales Límite: Animals / Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de IgG / Anticuerpos Monoclonales de Origen Murino / Anticuerpos Monoclonales Límite: Animals / Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos