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Programed death-1/programed death-ligand 1 expression in lymph nodes of HIV infected patients: results of a pilot safety study in rhesus macaques using anti–programed death-ligand 1 (Avelumab)
The programed death-1 (PD1)/programed death-ligand 1 (PD-L1) pathway plays a critical role in balancing immunity and host immunopathology. During chronic HIV/SIV infection, there is persistent immune activation accompanied by accumulation of virus-specific cells with terminally differentiated phenot...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5051527/ https://www.ncbi.nlm.nih.gov/pubmed/27490642 http://dx.doi.org/10.1097/QAD.0000000000001217 |
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author | Gill, Amanda L. Green, Samantha A. Abdullah, Shahed Le Saout, Cecile Pittaluga, Stefania Chen, Hui Turnier, Refika Lifson, Jeffrey Godin, Steven Qin, Jing Sneller, Michael C. Cuillerot, Jean-Marie Sabzevari, Helen Lane, H. Clifford Catalfamo, Marta |
author_facet | Gill, Amanda L. Green, Samantha A. Abdullah, Shahed Le Saout, Cecile Pittaluga, Stefania Chen, Hui Turnier, Refika Lifson, Jeffrey Godin, Steven Qin, Jing Sneller, Michael C. Cuillerot, Jean-Marie Sabzevari, Helen Lane, H. Clifford Catalfamo, Marta |
author_sort | Gill, Amanda L. |
collection | PubMed |
description | The programed death-1 (PD1)/programed death-ligand 1 (PD-L1) pathway plays a critical role in balancing immunity and host immunopathology. During chronic HIV/SIV infection, there is persistent immune activation accompanied by accumulation of virus-specific cells with terminally differentiated phenotypes and expression of regulatory receptors such as PD1. These observations led us to hypothesize that the PD1/PD-L1 pathway contributes to the functional dysregulation and ineffective viral control, and its blockade may be a potential immunotherapeutic target. METHODS: Lymph node biopsies from HIV-infected patients (n = 23) were studied for expression of PD1 and PD-L1. In addition, we assessed the safety and biological activity of a human anti-PD-L1 antibody (Avelumab) in chronically SIV-infected rhesus macaques. RESULTS: PD-L1 expression was observed in cells with myloid/macrophage morphology in HIV-infected lymph nodes. Administration of anti-PD-L1 was well tolerated, and no changes in body weights, hematologic, or chemistry parameters were observed during the study. Blockade of PD-L1 led to a trend of transient viral control after discontinuation of treatment. CONCLUSION: Administration of anti-PD-L1 in chronic SIV-infected rhesus macaques was well tolerated. Overall, these data warrant further investigation to assess the efficacy of anti-PD-L1 treatment on viral control in chronic SIV infection as a prelude to such therapy in humans. |
format | Online Article Text |
id | pubmed-5051527 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-50515272016-11-01 Programed death-1/programed death-ligand 1 expression in lymph nodes of HIV infected patients: results of a pilot safety study in rhesus macaques using anti–programed death-ligand 1 (Avelumab) Gill, Amanda L. Green, Samantha A. Abdullah, Shahed Le Saout, Cecile Pittaluga, Stefania Chen, Hui Turnier, Refika Lifson, Jeffrey Godin, Steven Qin, Jing Sneller, Michael C. Cuillerot, Jean-Marie Sabzevari, Helen Lane, H. Clifford Catalfamo, Marta AIDS Clinical Science: Concise Communication The programed death-1 (PD1)/programed death-ligand 1 (PD-L1) pathway plays a critical role in balancing immunity and host immunopathology. During chronic HIV/SIV infection, there is persistent immune activation accompanied by accumulation of virus-specific cells with terminally differentiated phenotypes and expression of regulatory receptors such as PD1. These observations led us to hypothesize that the PD1/PD-L1 pathway contributes to the functional dysregulation and ineffective viral control, and its blockade may be a potential immunotherapeutic target. METHODS: Lymph node biopsies from HIV-infected patients (n = 23) were studied for expression of PD1 and PD-L1. In addition, we assessed the safety and biological activity of a human anti-PD-L1 antibody (Avelumab) in chronically SIV-infected rhesus macaques. RESULTS: PD-L1 expression was observed in cells with myloid/macrophage morphology in HIV-infected lymph nodes. Administration of anti-PD-L1 was well tolerated, and no changes in body weights, hematologic, or chemistry parameters were observed during the study. Blockade of PD-L1 led to a trend of transient viral control after discontinuation of treatment. CONCLUSION: Administration of anti-PD-L1 in chronic SIV-infected rhesus macaques was well tolerated. Overall, these data warrant further investigation to assess the efficacy of anti-PD-L1 treatment on viral control in chronic SIV infection as a prelude to such therapy in humans. Lippincott Williams & Wilkins 2016-10-23 2016-09-28 /pmc/articles/PMC5051527/ /pubmed/27490642 http://dx.doi.org/10.1097/QAD.0000000000001217 Text en Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. http://creativecommons.org/licenses/by/4.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by/4.0 |
spellingShingle | Clinical Science: Concise Communication Gill, Amanda L. Green, Samantha A. Abdullah, Shahed Le Saout, Cecile Pittaluga, Stefania Chen, Hui Turnier, Refika Lifson, Jeffrey Godin, Steven Qin, Jing Sneller, Michael C. Cuillerot, Jean-Marie Sabzevari, Helen Lane, H. Clifford Catalfamo, Marta Programed death-1/programed death-ligand 1 expression in lymph nodes of HIV infected patients: results of a pilot safety study in rhesus macaques using anti–programed death-ligand 1 (Avelumab) |
title | Programed death-1/programed death-ligand 1 expression in lymph nodes of HIV infected patients: results of a pilot safety study in rhesus macaques using anti–programed death-ligand 1 (Avelumab) |
title_full | Programed death-1/programed death-ligand 1 expression in lymph nodes of HIV infected patients: results of a pilot safety study in rhesus macaques using anti–programed death-ligand 1 (Avelumab) |
title_fullStr | Programed death-1/programed death-ligand 1 expression in lymph nodes of HIV infected patients: results of a pilot safety study in rhesus macaques using anti–programed death-ligand 1 (Avelumab) |
title_full_unstemmed | Programed death-1/programed death-ligand 1 expression in lymph nodes of HIV infected patients: results of a pilot safety study in rhesus macaques using anti–programed death-ligand 1 (Avelumab) |
title_short | Programed death-1/programed death-ligand 1 expression in lymph nodes of HIV infected patients: results of a pilot safety study in rhesus macaques using anti–programed death-ligand 1 (Avelumab) |
title_sort | programed death-1/programed death-ligand 1 expression in lymph nodes of hiv infected patients: results of a pilot safety study in rhesus macaques using anti–programed death-ligand 1 (avelumab) |
topic | Clinical Science: Concise Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5051527/ https://www.ncbi.nlm.nih.gov/pubmed/27490642 http://dx.doi.org/10.1097/QAD.0000000000001217 |
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