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Your search keyword '"Nawaf, Maher G."' showing total 2 results
Start Over Author "Nawaf, Maher G." Topic programmed cell death 1 receptor
2 results on '"Nawaf, Maher G."'

1. Concurrent OX40 and CD30 Ligand Blockade Abrogates the CD4-Driven Autoimmunity Associated with CTLA4 and PD1 Blockade while Preserving Excellent Anti-CD8 Tumor Immunity.

Author

Nawaf MG, Ulvmar MH, Withers DR, McConnell FM, Gaspal FM, Webb GJ, Jones ND, Yagita H, Allison JP, and Lane PJL

Subjects
Animals, CD30 Ligand immunology, CTLA-4 Antigen immunology, Forkhead Transcription Factors deficiency, Forkhead Transcription Factors genetics, Forkhead Transcription Factors metabolism, Immunotherapy, Ligands, Lymphocyte Activation, Mice, Mice, Knockout, Neoplasms therapy, Programmed Cell Death 1 Receptor immunology, Receptors, OX40 immunology, T-Lymphocytes, Regulatory immunology, Autoimmunity, CD30 Ligand antagonists & inhibitors, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, CTLA-4 Antigen antagonists & inhibitors, Neoplasms immunology, Programmed Cell Death 1 Receptor antagonists & inhibitors, Receptors, OX40 antagonists & inhibitors
Abstract

Although strategies that block FOXP3-dependent regulatory T cell function (CTLA4 blockade) and the inhibitory receptor PD1 have shown great promise in promoting antitumor immune responses in humans, their widespread implementation for cancer immunotherapy has been hampered by significant off-target autoimmune side effects that can be lethal. Our work has shown that absence of OX40 and CD30 costimulatory signals prevents CD4 T cell-driven autoimmunity in Foxp3-deficient mice, suggesting a novel way to block these side effects. In this study, we show that excellent antitumor CD8 T cell responses can be achieved in Foxp3 KO mice deficient in OX40 and CD30 signals, particularly in the presence of concurrent PD1 blockade. Furthermore, excellent antitumor immune responses can also be achieved using combinations of Abs that block CTLA4, PD1, OX40, and CD30 ligands, without CD4 T cell-driven autoimmunity. By dissociating autoimmune side effects from anticancer immune responses, this potentially shifts this antitumor approach to patients with far less advanced disease., (Copyright © 2017 The Authors.)

Published
2017
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2. Concurrent OX40 and CD30 Ligand Blockade Abrogates the CD4-Driven Autoimmunity Associated with CTLA4 and PD1 Blockade while Preserving Excellent Anti-CD8 Tumor Immunity

Author

Nawaf, Maher G., Ulvmar, Maria H., Withers, David R., McConnell, Fiona M., Gaspal, Fabrina M., Webb, Gwilym J., Jones, Nick D., Yagita, Hideo, Allison, James P., and Lane, Peter J. L.

Subjects
CD4-Positive T-Lymphocytes, Mice, Knockout, Programmed Cell Death 1 Receptor, Immunology in the medical area, Autoimmunity, Forkhead Transcription Factors, chemical and pharmacologic phenomena, CD8-Positive T-Lymphocytes, Receptors, OX40, Ligands, Lymphocyte Activation, T-Lymphocytes, Regulatory, Mice, Neoplasms, Immunologi inom det medicinska området, Animals, CTLA-4 Antigen, Immunotherapy, CD30 Ligand, Immunotherapy and Vaccines
Abstract

Although strategies that block FOXP3-dependent regulatory T cell function (CTLA4 blockade) and the inhibitory receptor PD1 have shown great promise in promoting antitumor immune responses in humans, their widespread implementation for cancer immunotherapy has been hampered by significant off-target autoimmune side effects that can be lethal. Our work has shown that absence of OX40 and CD30 costimulatory signals prevents CD4 T cell-driven autoimmunity in Foxp3-deficient mice, suggesting a novel way to block these side effects. In this study, we show that excellent antitumor CD8 T cell responses can be achieved in Foxp3(KO) mice deficient in OX40 and CD30 signals, particularly in the presence of concurrent PD1 blockade. Furthermore, excellent antitumor immune responses can also be achieved using combinations of Abs that block CTLA4, PD1, OX40, and CD30 ligands, without CD4 T cell-driven autoimmunity. By dissociating autoimmune side effects from anticancer immune responses, this potentially shifts this antitumor approach to patients with far less advanced disease.

Published
2017

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