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

نویسندگان

  • Frederick Arce Vargas
  • Andrew J.S. Furness
  • Isabelle Solomon
  • 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
  • Lavinia Spain
  • Andrew Wotherspoon
  • Nicholas Francis
  • Myles Smith
  • Dirk Strauss
  • Andrew Hayes
  • Aspasia Soultati
  • Mark Stares
  • Joanna Lynch
  • Nicos Fotiadis
  • Archana Fernando
  • Steve Hazell
  • Ashish Chandra
  • Lisa Pickering
  • Sarah Rudman
  • Simon Chowdhury
  • Charles Swanton
  • 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 Wilson
  • Nicolai J. Birkbak
  • Thomas B.K. Watkins
  • Nicholas McGranahan
  • Stuart Horswell
  • Richard Mitter
  • Mickael Escudero
  • Aengus Stewart
  • Peter Van Loo
  • Andrew Rowan
  • Hang Xu
  • Samra Turajlic
  • Crispin 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 L. 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 Taylor
  • Rajesh Shah
  • Piotr Krysiak
  • Kendadai Rammohan
  • Eustace Fontaine
  • Richard Booton
  • Matthew Evison
  • Phil Crosbie
  • Stuart Moss
  • Faiza Idries
  • Leena Joseph
  • Paul Bishop
  • Anshuman Chaturved
  • Anne Marie Quinn
  • Helen Doran
  • Angela Leek
  • Phil Harrison
  • Katrina Moore
  • Rachael Waddington
  • Juliette Novasio
  • Fiona 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 Fennell
  • Jacqui A. Shaw
  • John Le Quesne
  • David Moore
  • Apostolos Nakas
  • Sridhar Rathinam
  • William Monteiro
  • Hilary Marshall
  • Louise Nelson
  • Jonathan Bennett
  • Joan Riley
  • Lindsay Primrose
  • Luke Martinson
  • Girija Anand
  • Sajid Khan
  • Anita Amadi
  • Marianne Nicolson
  • Keith Kerr
  • Shirley Palmer
  • Hardy Remmen
  • Joy Miller
  • Keith Buchan
  • Mahendran Chetty
  • Lesley Gomersall
  • Jason Lester
  • Alison 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 Smith
  • Nicole Gower
  • Christian Ottensmeier
  • Serena Chee
  • Benjamin Johnson
  • Aiman Alzetani
  • Emily Shaw
  • Eric Lim
  • Paulo De Sousa
  • Monica Tavares Barbosa
  • Alex Bowman
  • Simon Jorda
  • Alexandra Rice
  • Hilgardt 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 Edwards
  • Jennifer Hill
  • Sue Matthews
  • Yota Kitsanta
  • Kim Suvarna
  • Patricia Fisher
  • Allah Dino Keerio
  • Michael Shackcloth
  • John Gosney
  • Pieter Postmus
  • Sarah Feeney
  • Julius Asante-Siaw
  • Samra Turajlic
  • Martin Gore
  • James Larkin
  • Charles Swanton
  • Kerry A. Chester
  • Martin Pule
  • Jeffrey V. Ravetch
  • Teresa Marafioti
  • Karl S. Peggs
  • Sergio A. Quezada
چکیده

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.

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عنوان ژورنال:

دوره 46  شماره 

صفحات  -

تاریخ انتشار 2017