Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors.
Frederick Arce Vargas,Andrew Furness,Andrew Furness,Isabelle Solomon,Kroopa Joshi,Kroopa Joshi,Leila Mekkaoui,Marta H. Lesko,Enrique Miranda Rota,Rony Dahan,Andrew Georgiou,Anna Sledzinska,Assma Ben Aissa,Dafne Franz,Mariana Werner Sunderland,Yien Ning Sophia Wong,Jake Y. Henry,Tim O'Brien,David Nicol,Ben Challacombe,Stephen A. Beers,Samra Turajlic,Martin Gore,James Larkin,Charles Swanton,Kerry A. Chester,Martin Pule,Jeffrey V. Ravetch,Teresa Marafioti,Karl S. Peggs,Sergio A. Quezada,Lavinia Spain,Andrew Wotherspoon,Nicholas Francis,Myles Smith,Dirk C. Strauss,Andrew J. Hayes,Aspasia Soultati,Mark Stares,Joanna Lynch,Nicos Fotiadis,Archana Fernando,Steve Hazell,Ashish Chandra,Lisa Pickering,Sarah Rudman,Simon Chowdhury,Mariam Jamal-Hanjani,Selvaraju Veeriah,Seema Shafi,Justyna Czyzewska-Khan,Diana Johnson,Joanne Laycock,Leticia Bosshard-Carter,Gerald Goh,Rachel Rosenthal,Pat Gorman,Nirupa Murugaesu,Robert E. Hynds,Gareth A. Wilson,Nicolai Juul Birkbak,Thomas B.K. Watkins,Nicholas McGranahan,Stuart Horswell,Richard Mitter,Mickael Escudero,Aengus Stewart,Peter Van Loo,Andrew Rowan,Hang Xu,Crispin T. Hiley,Christopher Abbosh,Jacki Goldman,Richard Kevin Stone,Tamara Denner,Nik Matthews,Greg Elgar,Sophia Ward,Jennifer Biggs,Marta Costa,Sharmin Begum,Ben Phillimore,Tim Chambers,Emma Nye,Sofia Graca,Maise Al Bakir,John A. Hartley,Helen Lowe,Javier Herrero,David Lawrence,Martin Hayward,Nikolaos Panagiotopoulos,Shyam Kolvekar,Mary Falzon,Elaine Borg,Celia Simeon,Gemma Hector,Amy Smith,Marie Aranda,Marco Novelli,Dahmane Oukrif,Sam M. Janes,Ricky Thakrar,Martin Forster,Tanya Ahmad,Siow Ming Lee,Dionysis Papadatos-Pastos,Dawn Carnell,Ruheena Mendes,Jeremy George,Neal Navani,Asia Ahmed,Magali Taylor,Junaid Choudhary,Yvonne Summers,Raffaele Califano,Paul D. Taylor,Rajesh Shah,Piotr Krysiak,Kendadai Rammohan,Eustace Fontaine,Richard Booton,Matthew Evison,Phil Crosbie,Stuart Moss,Faiza Idries,Leena Dennis Joseph,Paul N. Bishop,Anshuman Chaturved,Anne Marie Quinn,H. Doran,Angela Leek,Phil Harrison,Katrina Moore,Rachael Waddington,Juliette Novasio,Fiona H Blackhall,Jane Rogan,Elaine Smith,Caroline Dive,Jonathan Tugwood,Ged Brady,Dominic G. Rothwell,Francesca Chemi,Jackie Pierce,Sakshi Gulati,Babu Naidu,Gerald Langman,Simon Trotter,Mary Bellamy,Hollie Bancroft,Amy Kerr,Salma Kadiri,Joanne Webb,Gary Middleton,Madava Djearaman,Dean A. Fennell,Jacqui Shaw,John Le Quesne,David A. Moore,Apostolos Nakas,Sridhar Rathinam,William Monteiro,Hilary Marshall,Louise Nelson,Jonathan Bennett,Joan Riley,Lindsay Primrose,Luke Martinson,Girija Anand,Sajid A. Khan,Anita Amadi,Marianne Nicolson,Keith M. Kerr,Shirley Palmer,Hardy Remmen,Joy Miller,Keith Buchan,Mahendran Chetty,Lesley Gomersall,Jason F. Lester,A Edwards,Fiona Morgan,Haydn Adams,Helen Davies,Malgorzata Kornaszewska,Richard Attanoos,Sara Lock,Azmina Verjee,Mairead MacKenzie,Maggie Wilcox,Harriet Bell,Natasha Iles,Allan Hackshaw,Yenting Ngai,Sean W. Smith,N.H. Gower,Christian H. Ottensmeier,Serena Chee,Benjamin Johnson,Aiman Alzetani,Emily Shaw,Eric Lim,Paulo Loureiro de Sousa,Monica Tavares Barbosa,Alex Bowman,Simon Jorda,Alexandra Rice,H. Raubenheimer,Chiara Proli,Maria Elena Cufari,John Carlo Ronquillo,Angela Kwayie,Harshil Bhayani,Morag Hamilton,Yusura Bakar,Natalie Mensah,Lyn Ambrose,Anand Devaraj,Silviu Buderi,Jonathan Finch,Leire Azcarate,Hema Chavan,Sophie Green,Hillaria Mashinga,Andrew G. Nicholson,Kelvin Lau,Michael Sheaff,Peter Schmid,John Conibear,Veni Ezhil,Babikir Ismail,Melanie Irvin-Sellers,Vineet Prakash,Peter Russell,Teresa Light,Tracey Horey,Sarah Danson,Jonathan Bury,John G. Edwards,Jennifer Hill,S. Matthews,Yota Kitsanta,Kim Suvarna,Patricia Fisher,Allah Dino Keerio,Michael Shackcloth,John Gosney,Pieter E. Postmus,Sarah Feeney,Julius Asante-Siaw +250 more
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TLDR
Use of an anti‐CD25 antibody with enhanced binding to activating Fc&ggr;Rs led to effective depletion of tumor‐infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors.About:
This article is published in Immunity.The article was published on 2017-04-18 and is currently open access. It has received 315 citations till now. The article focuses on the topics: IL-2 receptor & Cancer immunotherapy.read more
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Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells.
Zhiwei Zhou,Huabin He,Kun Wang,Xuyan Shi,Yupeng Wang,Ya Su,Yao Wang,Da Li,Wang Liu,Yongliang Zhang,Lianjun Shen,Weidong Han,Lin Shen,Jingjin Ding,Feng Shao +14 more
TL;DR: It is shown that granzyme A cleaves and activates gasdermin B (GSDMB), a central player in the highly inflammatory cell death process known as pyroptosis, suggesting that this pathway may be a target for future cancer immunotherapies.
Journal ArticleDOI
Combination Cancer Therapy with Immune Checkpoint Blockade: Mechanisms and Strategies.
Shetal A. Patel,Andy J. Minn +1 more
TL;DR: A framework for rationally designing combination therapy strategies based on enhancing major discriminatory functions of the immune system that are corrupted by cancer-namely, antigenicity, adjuvanticity, and homeostatic feedback inhibition is discussed.
Journal ArticleDOI
Genetics and biology of prostate cancer.
TL;DR: Improved disease management will also benefit from artificial intelligence-based expert decision support systems for proper standard of care, prognostic determinant biomarkers to minimize overtreatment of localized disease, and new standards of care accelerated by next-generation adaptive clinical trials.
Journal ArticleDOI
Human FOXP3+ Regulatory T Cell Heterogeneity and Function in Autoimmunity and Cancer
TL;DR: Findings within the context of concepts in Treg cell development and function derived from preclinical models and insight from approaches targeting Treg cells in clinical settings are discussed.
Journal ArticleDOI
CD4 and CD8 T lymphocyte interplay in controlling tumor growth
TL;DR: An overview of T lymphocyte-driven control of tumor growth is given and the involved tumor-suppressive mechanisms of the immune system, such as senescence surveillance, cancer immunosurveillance, and cancer immunoediting are discussed with respect to recent clinical developments of immunotherapies.
References
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Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma.
James Larkin,Vanna Chiarion-Sileni,Rene Gonzalez,Jean-Jacques Grob,C. Lance Cowey,Christopher D. Lao,Dirk Schadendorf,Reinhard Dummer,Michael Smylie,Piotr Rutkowski,Pier Francesco Ferrucci,A. Hill,John Wagstaff,Matteo S. Carlino,John B A G Haanen,Michele Maio,Ivan Marquez-Rodas,Grant A. McArthur,Paolo A. Ascierto,Georgina V. Long,Margaret K. Callahan,Michael A. Postow,Michael A. Postow,Kenneth F. Grossmann,Mario Sznol,Brigitte Dréno,Lars Bastholt,Arvin Yang,Linda Rollin,Christine Horak,F. Stephen Hodi,Jedd D. Wolchok,Jedd D. Wolchok +32 more
TL;DR: Among previously untreated patients with metastatic melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipILimumab alone, and in patients with PD-L1-negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone.
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Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.
TL;DR: The authors showed that CD4+CD25+ cells contribute to maintaining self-tolerance by downregulating immune response to self and non-self Ags in an Ag-nonspecific manner, presumably at the T cell activation stage.
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Immune checkpoint blockade: a common denominator approach to cancer therapy
TL;DR: The immune system recognizes and is poised to eliminate cancer but is held in check by inhibitory receptors and ligands, so drugs interrupting immune checkpoints, such as anti-CTLA-4, anti-PD-1, and others in early development, can unleash anti-tumor immunity and mediate durable cancer regressions.
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Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets.
TL;DR: It is demonstrated that Fc-receptor-dependent mechanisms contribute substantially to the action of cytotoxic antibodies against tumors and indicate that an optimal antibody against tumors would bind preferentially to activation Fc receptors and minimally to the inhibitory partner FcγRIIB.
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Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma.
TL;DR: The authors’ full names, academic de‐ grees, and affiliations are listed in the Ap‐ pendix.
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