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Publication Number
US-12303552-B2
Publication Date
2025-05-20
Expiration Date
Abstract
An IL-15 super agonist (IL-15N72D:IL-15RαSU/IgGIFc; N-803) increases circulating NK cells, effector memory and effector memory RA cells in post-allogeneic hematopoietic stem cell transplant patients (HCT). Methods of treatment include administration of N-803 to subjects in need of such treatment.
Core Innovation
The invention relates to a method of modulating an immune response in an immunosuppressed subject by administering a therapeutically effective amount of an IL-15:IL-15Rα complex. The IL-15:IL-15Rα complex modulates amounts of circulating immune effector cells and/or immune effector cell activity, and activates immune effector cells. The immune effector cells comprise CD45RA−/CCR7− effector memory (T_EM) T cells or CD45RA+/CCR7− effector memory RA (T_EMRA) T cells.
The invention addresses immunosuppression in subjects, including subjects after allogeneic hematopoietic stem cell transplant (HCT), by using an IL-15 superagonist complex identified as N-803 (IL-15N72D:IL-15RαSu/Fc). The disclosed effects include changes in circulating NK and effector memory/EMRA T-cell populations. The disclosed immune modulation is described as improving immune effector cell activity and activation in the immunosuppressed setting.
The disclosed approach is also presented in the context of virus-infected subjects, including JC polyomavirus-associated progressive multifocal leukoencephalopathy (PML) and HIV infection. In the disclosed examples, N-803 is associated with decreased JC polyomavirus (JCV) DNA copies and improved MRI/neuro outcomes in a post-HCT case without GVHD, and with immune activation/proliferation and HIV transcription induction in a Phase I HIV study. The disclosed outcomes also include reduced inducible HIV reservoir and tolerability, including no IL-15 antibody formation and no IL-15-related cytokine side effects.
Claims Coverage
The document’s independent claim covers a method that administers an IL-15:IL-15Rα complex to an immunosuppressed subject to modulate circulating immune effector cells and/or immune effector cell activity, including activation of specified effector-memory T-cell phenotypes. The coverage is anchored on multiple independent clinical/immunological effects while dependent claims refine the IL-15:IL-15Rα complex, administration, dosing, and downstream outcomes.
Administering an IL-15:IL-15Rα complex to modulate immune responses
A method of modulating an immune response in an immunosuppressed subject by administering a therapeutically effective amount of an IL-15:IL-15Rα complex, wherein the IL-15:IL-15Rα complex modulates amounts of circulating immune effector cells, immune effector cell activity, and/or activates immune effector cells.
Activating effector memory T cells defined by CD45RA/CCR7 phenotype
The immune effector cells comprise CD45RA−/CCR7− effector memory (T_EM) T cells or CD45RA+/CCR7− effector memory RA (T_EMRA) T cells, as part of the IL-15:IL-15Rα complex–mediated immune modulation.
Overall, the claim coverage centers on administering a therapeutically effective IL-15:IL-15Rα complex to an immunosuppressed subject to modulate circulating immune effector cell amounts and/or activity and to activate immune effector cells, with explicit inclusion of CD45RA−/CCR7− T_EM and/or CD45RA+/CCR7− T_EMRA T-cell phenotypes.
Stated Advantages
In a post-HCT case, improved JC polyomavirus-associated PML outcomes, including decreased JCV DNA copies and MRI/neuro improvement without GVHD.
In a Phase I HIV study, immune activation/proliferation and HIV transcription induction are supported, and the inducible HIV reservoir is reduced.
Tolerated dosing up to 6 mcg/kg, with no IL-15 antibody formation and no IL-15-related cytokine side effects.
Documented Applications
Treatment/modulation of immune response in immunosuppressed subjects, including post-allogeneic HCT patients.
Treatment/modulation in virus-infected subjects, including JC polyomavirus-associated progressive multifocal leukoencephalopathy (PML).
Treatment/modulation in HIV infection, including immune activation/proliferation and reduction of inducible HIV reservoir as described in a Phase I HIV study.
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