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

Lesko, Marta H. ; Miranda Rota, Enrique ; Dahan, Rony ; Georgiou, Andrew ; Sledzinska, Anna ; Werner Sunderland, Mariana ; Nicol, David ; Beers, Stephen A. ; Wotherspoon, Andrew ; Hayes, Andrew ; Stares, Mark ; Pickering, Lisa ; Rudman, Sarah ; Veeriah, Selvaraju ; Shafi, Seema ; Laycock, Joanne ; Bosshard-Carter, Leticia ; Goh, Gerald ; Rosenthal, Rachel ; Hynds, Robert E. ; Birkbak, Nicolai J. ; McGranahan, Nicholas ; Mitter, Richard ; Stewart, Aengus ; Rowan, Andrew ; Turajlic, Samra ; Abbosh, Christopher ; Goldman, Jacki ; Denner, Tamara ; Ward, Sophia ; Costa, Marta ; Lowe, Helen L. ; Lawrence, David ; Kolvekar, Shyam ; Falzon, Mary ; Simeon, Celia ; Hector, Gemma ; Novelli, Marco ; Forster, Martin ; Papadatos-Pastos, Dionysis ; Carnell, Dawn ; Navani, Neal ; Ahmed, Asia ; Taylor, Magali ; Choudhary, Junaid ; Taylor, Paul ; Rammohan, Kendadai ; Fontaine, Eustace ; Booton, Richard ; Moss, Stuart ; Idries, Faiza ; Joseph, Leena ; Moore, Katrina ; Waddington, Rachael ; Novasio, Juliette ; Blackhall, Fiona ; Rogan, Jane ; Tugwood, Jonathan ; Rothwell, Dominic G. ; Pierce, Jackie ; Gulati, Sakshi ; Kerr, Amy ; Webb, Joanne ; Moore, David ; Monteiro, William ; Marshall, Hilary ; Nelson, Louise ; Amadi, Anita ; Remmen, Hardy ; Miller, Joy ; Morgan, Fiona ; Kornaszewska, Malgorzata ; Bell, Harriet ; Smith, Sean ; Johnson, Benjamin ; Lim, Eric ; Barbosa, Monica Tavares ; Bowman, Alex ; Ronquillo, John Carlo ; Bhayani, Harshil ; Hamilton, Morag ; Bakar, Yusura ; Mensah, Natalie ; Buderi, Silviu ; Finch, Jonathan ; Green, Sophie ; Nicholson, Andrew G. ; Lau, Kelvin ; Schmid, Peter ; Conibear, John ; Ezhil, Veni ; Ismail, Babikir ; Prakash, Vineet ; Horey, Tracey ; Swanton, Charles ; Chester, Kerry A. ; Ravetch, Jeffrey V. ; Marafioti, Teresa ; Peggs, Karl S. ; Quezada, Sergio A.

Immunity (Cambridge, Mass.), 2017-04, Vol.46 (4), p.577-586 [Periódico revisado por pares]

United States: Elsevier Inc

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Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors
Autor: Lesko, Marta H. ; Miranda Rota, Enrique ; Dahan, Rony ; Georgiou, Andrew ; Sledzinska, Anna ; Werner Sunderland, Mariana ; Nicol, David ; Beers, Stephen A. ; Wotherspoon, Andrew ; Hayes, Andrew ; Stares, Mark ; Pickering, Lisa ; Rudman, Sarah ; Veeriah, Selvaraju ; Shafi, Seema ; Laycock, Joanne ; Bosshard-Carter, Leticia ; Goh, Gerald ; Rosenthal, Rachel ; Hynds, Robert E. ; Birkbak, Nicolai J. ; McGranahan, Nicholas ; Mitter, Richard ; Stewart, Aengus ; Rowan, Andrew ; Turajlic, Samra ; Abbosh, Christopher ; Goldman, Jacki ; Denner, Tamara ; Ward, Sophia ; Costa, Marta ; Lowe, Helen L. ; Lawrence, David ; Kolvekar, Shyam ; Falzon, Mary ; Simeon, Celia ; Hector, Gemma ; Novelli, Marco ; Forster, Martin ; Papadatos-Pastos, Dionysis ; Carnell, Dawn ; Navani, Neal ; Ahmed, Asia ; Taylor, Magali ; Choudhary, Junaid ; Taylor, Paul ; Rammohan, Kendadai ; Fontaine, Eustace ; Booton, Richard ; Moss, Stuart ; Idries, Faiza ; Joseph, Leena ; Moore, Katrina ; Waddington, Rachael ; Novasio, Juliette ; Blackhall, Fiona ; Rogan, Jane ; Tugwood, Jonathan ; Rothwell, Dominic G. ; Pierce, Jackie ; Gulati, Sakshi ; Kerr, Amy ; Webb, Joanne ; Moore, David ; Monteiro, William ; Marshall, Hilary ; Nelson, Louise ; Amadi, Anita ; Remmen, Hardy ; Miller, Joy ; Morgan, Fiona ; Kornaszewska, Malgorzata ; Bell, Harriet ; Smith, Sean ; Johnson, Benjamin ; Lim, Eric ; Barbosa, Monica Tavares ; Bowman, Alex ; Ronquillo, John Carlo ; Bhayani, Harshil ; Hamilton, Morag ; Bakar, Yusura ; Mensah, Natalie ; Buderi, Silviu ; Finch, Jonathan ; Green, Sophie ; Nicholson, Andrew G. ; Lau, Kelvin ; Schmid, Peter ; Conibear, John ; Ezhil, Veni ; Ismail, Babikir ; Prakash, Vineet ; Horey, Tracey ; Swanton, Charles ; Chester, Kerry A. ; Ravetch, Jeffrey V. ; Marafioti, Teresa ; Peggs, Karl S. ; Quezada, Sergio A.
Assuntos: Animals ; anti-CD25 ; anti-PD-1 ; Antibodies ; Antibodies, Monoclonal - immunology ; Antibodies, Monoclonal - metabolism ; Antibodies, Monoclonal - therapeutic use ; Anticancer properties ; Cancer ; Cancer immunotherapy ; CD25 ; Cell death ; Cell Line, Tumor ; Cytokines ; Depletion ; Fc gamma receptors ; Flow Cytometry ; Humans ; Immune response ; Immune system ; Immunoglobulin Fc Fragments - immunology ; Immunoglobulins ; Immunotherapy ; Immunotherapy - methods ; inhibitory Fc receptor ; Interleukin-2 Receptor alpha Subunit - immunology ; K562 Cells ; Kaplan-Meier Estimate ; Light emitting diodes ; Lymphatic system ; Lymphocyte Depletion ; Lymphocytes ; Lymphocytes T ; Melanoma ; Mice ; Neoplasms - immunology ; Neoplasms - pathology ; Neoplasms - therapy ; Programmed Cell Death 1 Receptor - antagonists & inhibitors ; Programmed Cell Death 1 Receptor - immunology ; Programmed Cell Death 1 Receptor - metabolism ; Protein Binding - immunology ; Receptors, IgG - immunology ; Receptors, IgG - metabolism ; regulatory T cells ; T-Lymphocytes, Regulatory - immunology ; T-Lymphocytes, Regulatory - metabolism ; Treg depletion ; tumor immunotherapy ; tumor microenvironment ; Tumors
É parte de: Immunity (Cambridge, Mass.), 2017-04, Vol.46 (4), p.577-586
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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These authors contributed equally
Descrição: 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. [Display omitted] •CD25 expression is largely restricted to Treg cells in mice and humans•FcγRIIb inhibits anti-CD25-mediated depletion of intra-tumoral Treg cells•Fc-optimized anti-CD25 efficiently depletes intra-tumoral Treg cells•Anti-CD25 synergizes with PD-1 blockade to reject established tumors Anti-CD25 antibodies have displayed only modest therapeutic activity against established tumors. Arce Vargas et al. demonstrate that existing anti-CD25 antibodies fail to deplete intra-tumoral Treg cells due to upregulation of FcγRIIb within tumors. Fc-optimized anti-CD25 mediates effective depletion of tumor-infiltrating Treg cells and synergizes with PD-1 blockade to promote tumor eradication.
Editor: United States: Elsevier Inc
Idioma: Inglês

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

United States: Elsevier Inc

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