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

  title={Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors},
  author={Frederick Arce Vargas and Andrew J.S. Furness and Isabelle Solomon and Kroopa Joshi and Leila Mekkaoui and Marta H. Lesko and Enrique Miranda Rota and Rony Dahan and Andrew Georgiou and Anna Śledzińska and Assma Ben Aissa and Dafne Franz and Mariana Werner Sunderland and Yien Ning Sophia Wong and Jake Y. Henry and Tim M. O’Brien and David G. Nicol and Ben J. Challacombe and Stephen A Beers and Martin E. Gore and James Larkin and Kerry Ann Chester and Martin Pule and Jeffrey V Ravetch and Teresa Marafioti and Karl S. Peggs and Sergio A Quezada and Andrew C. Wotherspoon and Nicholas Francis and Myles G. Smith and Dirk Strauss and Andrew Hayes and Aspasia S Soultati and Mark Stares and Lavinia Spain and Joanna Lynch and Nicos I. Fotiadis and Archana Fernando and Steve Hazell and Ashish Chandra and Lisa M. Pickering and Sarah Rudman and Simon Chowdhury and Charles Swanton and Mariam Jamal-Hanjani and Selvaraju Veeriah and Seema Shafi and Justyna Czyzewska-Khan and Diana Johnson and Joanne Laycock and Leticia Bosshard-Carter and Gerald Goh and Rachel Elizabeth Rosenthal and Pat Gorman and Nirupa Murugaesu and Robert E Hynds and Gareth A. Wilson and Nicolai J. Birkbak and Thomas B. K. Watkins and Nicholas McGranahan and Stuart D Horswell and Richard Mitter and Mickael Escudero and Aengus Stewart and Peter Van Loo and Andrew J. Rowan and Hang Xu and Samra Turajli{\'c} and Crispin T. Hiley and Christopher Abbosh and Jacki P. Goldman and Richard Kevin Stone and Tamara Denner and Nik Matthews and Greg Elgar and Sophia Ward and Jennifer Biggs and Marta Costa and Sharmin Begum and Ben Phillimore and Tim Chambers and Emma Dane Nye and Sofia Graça and Maise Al Bakir and John A. Hartley and Helen Laura Lowe and Javier Herrero Herrero and David Lawrence and Martin Hayward and Nikolaos Panagiotopoulos and Shyam K Kolvekar and Mary Falzon and Elaine Borg and Celia Simeon and G Cortes Torres Hector and Amy Lynn Smith and Marie Aranda and Marco Novelli and Dahmane Oukrif and Sam M Janes and Ricky Thakrar and Martin Forster and Tanya Ahmad and Siow Ming Lee and Dionysis Papadatos-Pastos and Dawn Carnell and Ruheena Mendes and Jeremy J. George and Neal Navani and Asia Mahgoub Taha Ahmed and Magali N Taylor and Junaid Choudhary and Yvonne Summers and Raffaele Califano and Paul Taylor and Rajesh Shah and Piotr Krysiak and Kendadai Rammohan and Eustace J Fontaine and Richard Booton and Matthew Evison and Phil Crosbie and Stuart Moss and Faiza Idries and Leena Joseph and Paul Burton Bishop and Anshuman Chaturved and Anne Marie K. Quinn and Helen Doran and Angela C. Leek and Phil M. Harrison and Katrina H. Moore and Rachael Waddington and Juliette Novasio and Fiona Blackhall and Jane Rogan and Elaine Claire Smith and Caroline Dive and Jonathan D. Tugwood and Ged Brady and Dominic G Rothwell and Francesca Chemi and Jackie A Pierce and Sakshi Gulati and Babu Naidu and Gerald Langman and Simon Trotter and Mary Bellamy and Hollie Bancroft and Amy Kerr and Salma Kadiri and Joanne Webb and Gary Middleton and Madava G. Djearaman and Dean Fennell and Jacqui A. Shaw and John Le Quesne and David A. Moore and Apostolos Nakas and Sridhar Rathinam and William Monteiro and Hilary Choreographer Marshall and Louise G. Lord Nelson and Jonathan William Peter Bennett and J. Riley and Lindsay Primrose and Luke Martinson and Girija Anand and Sajid Khan and Anita Amadi and Marianne Nicolson and Keith Kerr and Shirley Palmer and Hardy Remmen and Joy Anderson Miller and Keith G. Buchan and Mahendran Chetty and Lesley Gomersall and Jason Francis Lester and Alison Edwards and Fiona Morgan and H. Travers Adams and Helen Davies and Malgorzata Kornaszewska and Richard Attanoos and Sara Lock and Azmina Verjee and Mairead Mackenzie and Maggie Wilcox and Harriet Bell and Natasha Iles and Allan Hackshaw and Yenting Ngai and Sean W. Smith and Nicole Lee Gower and Christian H Ottensmeier and Serena J Chee and Benjamin Aaron Johnson and Aiman Alzetani and Emily Shaw and Eric Teik Chung Lim and Paulo De Sousa and Monica Tavares Barbosa and Alex D Bowman and Simon Jorda and Alexandra Rice and Hilgardt Raubenheimer and Chiara Proli and Maria Elena Cufari and John Carlo Ronquillo and Angela Kwayie and Harshil Bhayani and Morag Hamilton and Yusura Bakar and Natalie Mensah and Lyn R. Ambrose and Anand A. Devaraj and Silviu Ioan Buderi and Jonathan B. Finch and Leire Azc{\'a}rate and Hema L. Chavan and Sophie Green and Hillaria Mashinga and Andrew G. Nicholson and Kelvin Yao Ming. Lau and Michael Sheaff and P. T. J{\"u}rgen Schmid and John Conibear and Veni Ezhil and Babikir Ismail and Melanie Irvin-sellers and Vineet Prakash and Peter Russell and Teresa Light and Tracey Horey and Sarah Danson and Jonathan Bury and John Edwards and Jennifer Hill and Sue Matthews and Yota Kitsanta and Kim Suvarna and Patricia J. Fisher and Allah Dino Keerio and Michael J Shackcloth and John Gosney and Pieter E Postmus and Sarah L. Feeney},
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… CONTINUE READING

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Publications referenced by this paper.

Dendritic cell vaccination in combination with anti-CD25 monoclonal antibody treatment: a phase I/II study in metastatic melanoma patients.

  • Clinical cancer research : an official journal of the American Association for Cancer Research
  • 2010

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