Dataset Information

Recombinant Human Interleukin-15 and Anti-PD-L1 Combination Therapy Expands a CXCR3+PD1-/low CD8 T-Cell Subset in Simian Immunodeficiency Virus-Infected Rhesus Macaques.

ABSTRACT:

Background

The PD1/PD-L1 pathway contributes to the pathogenesis of human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection, and blockade of this pathway may have potential to restore immune function and promote viral control or elimination. In this study, we combined a checkpoint inhibitor anti-PD-L1 (Avelumab) and recombinant human interleukin-15 (rhIL-15) in SIV-infected rhesus macaques (RM).

Methods

The rhIL-15 was administered as continuous infusion in 2 cycles of 10 days in the context of weekly administration of anti-PD-L1 (Avelumab) in SIV-infected RM receiving combination antiretroviral therapy (cART). Safety, immunological parameters, and viral loads were monitored during the study.

Results

Administration of rhIL-15/anti-PD-L1 was safe and well tolerated. Treatment resulted in transient increases in proliferating (Ki67+) natural killer and CD8 T cells. In addition, treatment expanded a CXCR3+PD1-/low CD8 T-cell subset with the ability to secrete cytokines. Despite these effects, no changes in plasma viremia were observed after cART interruption.

Conclusions

Expansion of the CXCR3+PD1-/low CD8 T-cell subset with functional capacity and potential to traffic to sites of viral reservoirs in SIV-infected rhesus macaques had no demonstrable effect on plasma viremia after cART interruption.

SUBMITTER: Chen P

PROVIDER: S-EPMC7325617 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Recombinant Human Interleukin-15 and Anti-PD-L1 Combination Therapy Expands a CXCR3+PD1-/low CD8 T-Cell Subset in Simian Immunodeficiency Virus-Infected Rhesus Macaques.

Chen Ping P Chen Hui H Moussa Maha M Cheng Jie J Li Tong T Qin Jing J Lifson Jeffrey D JD Sneller Michael C MC Krymskaya Ludmila L Godin Steven S Lane H Clifford HC Catalfamo Marta M

The Journal of infectious diseases 20200201 4

<h4>Background</h4>The PD1/PD-L1 pathway contributes to the pathogenesis of human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection, and blockade of this pathway may have potential to restore immune function and promote viral control or elimination. In this study, we combined a checkpoint inhibitor anti-PD-L1 (Avelumab) and recombinant human interleukin-15 (rhIL-15) in SIV-infected rhesus macaques (RM).<h4>Methods</h4>The rhIL-15 was administered as continuous infusion i ...[more]

PMID: 31562760

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Dataset Information

Recombinant Human Interleukin-15 and Anti-PD-L1 Combination Therapy Expands a CXCR3+PD1-/low CD8 T-Cell Subset in Simian Immunodeficiency Virus-Infected Rhesus Macaques.

Background

Methods

Results

Conclusions

Publications

Recombinant Human Interleukin-15 and Anti-PD-L1 Combination Therapy Expands a CXCR3+PD1-/low CD8 T-Cell Subset in Simian Immunodeficiency Virus-Infected Rhesus Macaques.

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