HIV treatment compositions and methods
Inventors
Niazi, Kayvan • Safrit, Jeffrey • Lee, John H.
Assignees
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Publication Number
US-12303477-B2
Publication Date
2025-05-20
Expiration Date
Abstract
HIV treatment, and especially treatment of latent infected CD4 cells, can be significantly improved using a kick-and-kill approach that employs an immune stimulation component and/or HDAC inhibition as one treatment component, and that may also include a second component in which a vaccine composition, various NK cells, CAR-T cells, and/or broadly neutralizing antibodies are administered.
Core Innovation
The invention relates to a method of treating an individual carrying latent human immunodeficiency virus (HIV) infected cells by administering IL-15 or an enhanced immune stimulatory derivative thereof together with a broadly neutralizing anti-HIV antibody (bNAb). The approach combines immune stimulation with antibody-mediated targeting of HIV in the context of latent infection, using IL-15 as an immune-stimulatory component and a broadly neutralizing antibody as a second therapeutic component.
In the disclosed embodiments, IL-15 may be used directly or via an enhanced IL-15 derivative, including ALT-803 and an ALT-803-based immune stimulatory or targeted molecule (TxM). The invention further describes combinations that can optionally include histone deacetylase (HDAC) inhibitors, with named examples including vorinostat, panobinostat, valproic acid, and other specified HDAC inhibitors, to support an overall kick-and-kill concept in which latent-cell viral antigen expression is increased and then targeted for elimination.
The disclosed kill component includes immune effector mechanisms and compositions. The document describes vaccination compositions containing recombinant nucleic acids encoding HIV antigens, and it also describes immune effector cell approaches including NK cells, genetically modified NK cells, and CAR-T/target-activated NK variants characterized by chimeric antigen receptors whose ectodomains bind to specified targets such as CD2, CD20, and CD32.
Claims Coverage
The provided content includes one independent claim, with additional dependent refinements that specify particular co-therapies, targeting components, antibody candidates, vaccine composition types, and optional HDAC inhibitor timing relative to IL-15. Overall, the core claim centers on the combination of IL-15 (or an enhanced derivative) with a broadly neutralizing anti-HIV antibody (bNAb).
Administering il-15 with a broadly neutralizing anti-hiv antibody
A method of treating an individual carrying latent human immunodeficiency virus (HIV) infected cells, comprising administering IL-15 or an enhanced immune stimulatory derivative thereof, and a broadly neutralizing anti-HIV antibody (bNAb).
Selecting a bNAb from a specified antibody set
The method uses a bNAb selected from a specified set of listed antibodies, including PGT121, 10-1074, 10E8, 10E8v4-V5R-100cF, 2F5, 2G12, 3BNC117, CAP256-VRC26.25, N6, PG9, PGDM1400, VRC01, and VRC07-523.
Co-administering an hdac inhibitor
The method includes an epigenetic modulation component in which an HDAC inhibitor is one of the specified compounds including vorinostat, panobinostat, valproic acid, phenylbutyrate, entinostat, CI-994, mocetinostat, Viracta VRx-3996, dacinostat, pivanex, givinostat, or belinostat.
Hdac inhibitor timing relative to il-15
The method specifies administering an HDAC inhibitor at least 24 hours before or after IL-15 (or an enhanced immune stimulatory derivative thereof).
Administering a car-t cell with a defined car ectodomain binding specificity
The method further includes administering a CAR-T cell whose chimeric antigen receptor (CAR) ectodomain binds to CD2, CD20, or CD32.
Administering a vaccine composition containing a recombinant nucleic acid encoding hiv antigens
The method includes administering a bacterial, yeast, or viral vaccine composition containing a recombinant nucleic acid encoding at least one HIV antigen.
Across the provided independent claim and dependents, the inventive coverage is anchored in co-administering IL-15 (or an enhanced derivative) with a broadly neutralizing anti-HIV antibody, with further refinements that specify enumerated bNAb candidates, optional HDAC inhibitor selection and timing, optional CAR-T targeting via defined CAR ectodomain binding to CD2/CD20/CD32, and optional administration of vaccine compositions encoding HIV antigens.
Stated Advantages
Documented Applications
No documented applications found
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