I-110 Targeting the PD-1/PD-L1 pathway to achieve a functional cure for chronic infection

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Abstract

Methods:

Cryopreserved PBMCs were thawed and expression of PD-1 and PD-L1 was measured either directly ex vivo or following stimulation with virus-specific peptides. PBMCs were also tested in IFN-γ or IL-2 ELISpot assays to monitor for HIV and HBV-specific T cell responses in the presence or absence of PD-1 or PD-L1 blocking mAbs or isotype-matched control mAbs.

Results:

As was reported by other investigators, PD-1 was found to be upregulated on virus-specific T cells from subjects with chronic infection. In addition, monocytes from chronically-infected subjects expressed PD-L1, and this expression was up-regulated following stimulation with virus-specific peptides. HIV and HBV-specific T cell responses were enhanced by an anti-PD-L1 agonist antibody. However, preliminary data suggests that chronic PD-1/PD-L1 blockade can result in expanded but non-functional virus-specific T cell populations associated with up-regulation of co-inhibitory receptors.

Conclusions:

A limited course with a PD-1/PD-L1 blocking mAb may have utility in the treatment of chronic infection and could be an important component of a functional cure.

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