The use of PD-1, LAG-3 and TIGIT as biomarkers of HIV persistence during antiretroviral therapy
OHSU # 1914
Value Proposition: Antiretroviral therapy (ART) reduces HIV replication but does not cure HIV. The persistence of HIV in a small pool of long-lived latently infected resting CD4 T cells is a major barrier to viral eradication. Identification of cellular markers that are preferentially expressed at the surface of latently infected cells paves the way for the development of novel therapeutic strategies aimed at reducing the pool of latently infected cells in virally suppressed subjects, with the overreaching goal of curing HIV.
This technology fills the pressing need to identify latent stage cells infected with HIV.
Technology Information: Several immune checkpoint blockers (ICBs) have been shown to actively reduce T cell activation, proliferation and cytokine production in CD4+ T cells, thereby acting as negative regulators of T-cell activation. In particular, PD-1, LAG-3 and TIGIT have been identified as markers associated with incomplete CD4 T cell restoration and HIV persistence during ART. The present technology involves the surprising discovery relating to identifying a cell comprising a latent HIV nucleic acid by detecting one or more of PD-1, LAG-3 and TIGIT, alone or in combination with each other or any other marker.
The methods involve obtaining a biological sample from a subject comprising CD4+ T cells. The sample is contacted with a labeled antibody that is specific for PD-1, LAG-3, or TIGIT. The detected cell surface molecules thereby indicate that the CD4+ T cell comprises latent HIV nucleic acid.
The invention efficiently identifies cells latently infected with HIV allowing for cell sorting of the elusive population. The cells can then be used to screen test compounds for potential therapeutics that inhibit (or eliminate) cells latently infected with HIV.
Basic Market Information: Stimulated by new drug launches and the increasing prevalence of HIV, the combined sales value of anti-HIV drugs is expected to rise over 40% in the several years from $11.9 billion in 2013 to $16.8 billion in 2022.
PCT Application No. PCT/US14/65472
United States Patent Application No. 14/540,722
Licensing Opportunity: The patent rights are available for licensing.
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Director, Technology Transfer