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 antiprogramed death-ligand 1 (Avelumab)

Objective: 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 differenti...

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Veröffentlicht in:AIDS (London) 2016-10, Vol.30 (16), p.2487-2493
Hauptverfasser: 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
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container_end_page 2493
container_issue 16
container_start_page 2487
container_title AIDS (London)
container_volume 30
creator 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
description Objective: 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.
doi_str_mv 10.1097/QAD.0000000000001217
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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.</abstract><doi>10.1097/QAD.0000000000001217</doi></addata></record>
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source EZB-FREE-00999 freely available EZB journals; Journals@Ovid Complete
subjects Lentivirus
Macaca mulatta
Retroviridae
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 antiprogramed death-ligand 1 (Avelumab)
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