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).
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: aCMRS/Laboratory of Immunoregulation, NIAID bLaboratory of Pathology, NCI, NIH, Bethesda cClinical Support Laboratory, Leidos Biomedical Research, Inc. dAIDS and Cancer Virus Program, Retroviral Pathogenesis Section, Leidos Biomedical Research, Frederick National Laboratory, Frederick eSmithers Avanza Toxicology Services, Gaithersburg fBiostatistics Research Branch, DCR, NIAID, NIH, Bethesda, Maryland gEMD-Serono, Inc., Rockland hCompass Therapeutics, Cambridge, Massachusetts, USA. *Amanda L. Gill and Samantha A. Green contributed equally to the article.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Gill
authors.forename: Samantha A
authors.initials: SA
authors.lastname: Green
authors.forename: Shahed
authors.initials: S
authors.lastname: Abdullah
authors.forename: Cecile
authors.initials: C
authors.lastname: Le Saout
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Refika
authors.initials: R
authors.lastname: Turnier
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lifson
authors.forename: Steven
authors.initials: S
authors.lastname: Godin
authors.forename: Jing
authors.initials: J
authors.lastname: Qin
authors.forename: Michael C
authors.initials: MC
authors.lastname: Sneller
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Cuillerot
authors.forename: Helen
authors.initials: H
authors.lastname: Sabzevari
authors.forename: H Clifford
authors.initials: HC
authors.lastname: Lane
authors.forename: Marta
authors.initials: M
authors.lastname: Catalfamo
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D060890:B7-H1 Antigen / Q000032:analysis*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D015658:HIV Infections / Q000473:pathology*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects*; D008198:Lymph Nodes / Q000473:pathology*; D008253:Macaca mulatta; D010865:Pilot Projects; D061026:Programmed Cell Death 1 Receptor / Q000032:analysis*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D060890:B7-H1 Antigen; D007155:Immunologic Factors; D061026:Programmed Cell Death 1 Receptor; C000609138:avelumab