Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors.

Autor:	Arce Vargas F; Cancer Immunology Unit, University College London Cancer Institute, London WC1E 6DD, UK; Research Department of Haematology, UCL Cancer Institute, London WC1E 6DD, UK., Furness AJS; Cancer Immunology Unit, University College London Cancer Institute, London WC1E 6DD, UK; Research Department of Haematology, UCL Cancer Institute, London WC1E 6DD, UK; The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK., Solomon I; Cancer Immunology Unit, University College London Cancer Institute, London WC1E 6DD, UK; Research Department of Haematology, UCL Cancer Institute, London WC1E 6DD, UK., Joshi K; Cancer Immunology Unit, University College London Cancer Institute, London WC1E 6DD, UK; Research Department of Haematology, UCL Cancer Institute, London WC1E 6DD, UK; The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK., Mekkaoui L; Research Department of Oncology, UCL Cancer Institute, London WC1E 6DD, UK., Lesko MH; Cancer Immunology Unit, University College London Cancer Institute, London WC1E 6DD, UK; Research Department of Haematology, UCL Cancer Institute, London WC1E 6DD, UK., Miranda Rota E; Research Department of Oncology, UCL Cancer Institute, London WC1E 6DD, UK., Dahan R; Leonard Wagner Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10065, USA., Georgiou A; Cancer Immunology Unit, University College London Cancer Institute, London WC1E 6DD, UK; Research Department of Haematology, UCL Cancer Institute, London WC1E 6DD, UK., Sledzinska A; Cancer Immunology Unit, University College London Cancer Institute, London WC1E 6DD, UK; Research Department of Haematology, UCL Cancer Institute, London WC1E 6DD, UK., Ben Aissa A; Cancer Immunology Unit, University College London Cancer Institute, London WC1E 6DD, UK; Research Department of Haematology, UCL Cancer Institute, London WC1E 6DD, UK., Franz D; Cancer Immunology Unit, University College London Cancer Institute, London WC1E 6DD, UK; Research Department of Haematology, UCL Cancer Institute, London WC1E 6DD, UK., Werner Sunderland M; Cancer Immunology Unit, University College London Cancer Institute, London WC1E 6DD, UK; Research Department of Haematology, UCL Cancer Institute, London WC1E 6DD, UK., Wong YNS; Cancer Immunology Unit, University College London Cancer Institute, London WC1E 6DD, UK; Research Department of Haematology, UCL Cancer Institute, London WC1E 6DD, UK., Henry JY; Cancer Immunology Unit, University College London Cancer Institute, London WC1E 6DD, UK; Research Department of Haematology, UCL Cancer Institute, London WC1E 6DD, UK., O'Brien T; Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT, UK., Nicol D; The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK., Challacombe B; Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT, UK., Beers SA; Antibody and Vaccine Group, Cancer Sciences Unit, University of Southampton, Faculty of Medicine, Southampton SO17 1BJ, UK., Turajlic S; The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK; The Francis Crick Institute, London NW1 1AT, UK., Gore M; The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK., Larkin J; The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK., Swanton C; The Francis Crick Institute, London NW1 1AT, UK; Translational Cancer Therapeutics Laboratory, UCL Cancer Institute, London WC1E 6DD, UK., Chester KA; Research Department of Oncology, UCL Cancer Institute, London WC1E 6DD, UK., Pule M; Research Department of Haematology, UCL Cancer Institute, London WC1E 6DD, UK., Ravetch JV; Leonard Wagner Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 10065, USA., Marafioti T; Department of Cellular Pathology, University College London Hospital, London NW1 2BU, UK., Peggs KS; Cancer Immunology Unit, University College London Cancer Institute, London WC1E 6DD, UK; Research Department of Haematology, UCL Cancer Institute, London WC1E 6DD, UK. Electronic address: k.peggs@ucl.ac.uk., Quezada SA; Cancer Immunology Unit, University College London Cancer Institute, London WC1E 6DD, UK; Research Department of Haematology, UCL Cancer Institute, London WC1E 6DD, UK. Electronic address: s.quezada@ucl.ac.uk.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2017 Apr 18; Vol. 46 (4), pp. 577-586. Date of Electronic Publication: 2017 Apr 11.
DOI:	10.1016/j.immuni.2017.03.013
Abstrakt:	CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology. (Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu