Academic Journal
Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors.
| العنوان: | Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors. |
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| المؤلفون: | Arce Vargas, Frederick, Furness, Andrew J. S., Solomon, Isabelle, Joshi, Kroopa, Mekkaoui, Leila, Lesko, Marta H., Miranda Rota, Enrique, Dahan, Rony, Georgiou, Andrew, Sledzinska, Anna, Ben Aissa, Assma, Franz, Dafne, Werner Sunderland, Mariana, Wong, Yien Ning Sophia, Henry, Jake Y., O'Brien, Tim, Nicol, David, Challacombe, Ben, Beers, Stephen A., Melanoma TRACERx Consortium, Renal TRACERx Consortium, Lung TRACERx Consortium, Turajlic, Samra, Gore, Martin, Larkin, James, Swanton, Charles, Chester, Kerry A., Pule, Martin, Ravetch, Jeffrey V., Marafioti, Teresa, Peggs, Karl S., Quezada, Sergio A. |
| بيانات النشر: | Elsevier (Cell Press) |
| سنة النشر: | 2017 |
| المجموعة: | University of Leicester: Leicester Research Archive (LRA) |
| مصطلحات موضوعية: | CD25, Fc gamma receptors, Treg depletion, anti-CD25, anti-PD-1, inhibitory Fc receptor, regulatory T cells, tumor immunotherapy, tumor microenvironment, Animals, Antibodies, Monoclonal, Cell Line, Tumor, Flow Cytometry, Humans, Immunoglobulin Fc Fragments, Immunotherapy, Interleukin-2 Receptor alpha Subunit, K562 Cells, Kaplan-Meier Estimate, Lymphocyte Depletion, Mice, Neoplasms, Programmed Cell Death 1 Receptor, Protein Binding, Receptors, IgG, T-Lymphocytes, Regulatory |
| الوصف: | Supplemental Information includes four figures, four tables, Supplemental Experimental Procedures, and consortia memberships and can be found with this article online at http://dx.doi.org/10.1016/j.immuni.2017.03.013. ; 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. ; S.A.Q. is a Cancer Research U.K. (CRUK) Senior Fellow (C36463/A22246) and is funded by a Cancer Research Institute Investigator Award and a CRUK Biotherapeutic Program Grant (C36463/A20764). K.S.P. receives funding from the NIHR BTRU for Stem Cells and Immunotherapies (167097), of which he is the Scientific Director. None of the animal work described was funded by NIHR. This work was undertaken at UCL Hospitals/UCL with support from the CRUK-UCL Centre (C416/A18088), CRUK’s Lung Cancer Centre of Excellence (C5759/A20465), the CRUK and Engineering and Physical Sciences Research Council at King's College London and UCL (C1519/A16463), the Cancer Immunotherapy Accelerator Award (CITA-CRUK) (C33499/A20265), CRUK’s Lung TRACERx ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1074-7613 1097-4180 |
| Relation: | https://www.ncbi.nlm.nih.gov/pubmed/28410988; Immunity, 2017, 46 (4), pp. 577-586; http://www.sciencedirect.com/science/article/pii/S1074761317301231?via%3Dihub; http://hdl.handle.net/2381/40685; S1074-7613(17)30123-1 |
| DOI: | 10.1016/j.immuni.2017.03.013 |
| الاتاحة: | http://www.sciencedirect.com/science/article/pii/S1074761317301231?via%3Dihub http://hdl.handle.net/2381/40685 https://doi.org/10.1016/j.immuni.2017.03.013 |
| Rights: | Copyright © the authors, 2017. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| رقم الانضمام: | edsbas.AF85A159 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 10747613 10974180 |
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| DOI: | 10.1016/j.immuni.2017.03.013 |