Modulation of NK cell antigen specific effector activity by modulation of CXCR6 (CD186)
AssigneePresident and Fellows of Harvard College
InventorsUlrich Von Andrian, Silke Paust
Life of this patent
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Abstract
The instant invention is based, at least in part, on the discovery that CXCR6 plays a critical role in antigen-specific effector function of NK cells. Accordingly, the invention provides, among other things, methods for modulation of antigen-specific NK cell effector function, methods for identifying modulators of antigen-specific NK cell effector function.
Claims17
A method of decreasing antigen-specific NK cell function in a subject comprising:
- measuring antigen-specific NK cell function in the subject and comparing the level of antigen-specific NK cell function to an appropriate control;
- and
- administering to the subject having an increased level of antigen-specific NK cell function a composition comprising an antibody, or antigen-binding fragment thereof, that binds to an extracellular domain of human CXCR6 and blocks the binding of CXCR6 to the extracellular domain of CXCL16, such that antigen-specific NK cell function is decreased.
A method of decreasing antigen-specific NK cell function in a subject having unwanted immune cell activation, comprising:
- measuring antigen-specific NK cell function in the subject and comparing the level of antigen-specific NK cell function to an appropriate control;
- and
- administering to the subject having an increased level of antigen-specific NK cell function a composition comprising an antibody, or antigen-binding fragment thereof, that binds to the extracellular domain of CXCL16 and blocks the binding of CXCL16 with an extracellular domain of CXCR6, such that antigen-specific NK cell function is decreased.
A method of treating a subject having delayed-type hypersensitivity to an antigen, comprising:
- administering to the subject (i) a composition comprising an antibody, or antigen-binding fragment thereof, wherein the antibody, or antigen-binding fragment thereof, is selected from the group consisting of an antibody, or antigen-binding fragment thereof, that binds to the extracellular domain of CXCR6 and blocks the binding of CXCR6 to CXCL16, and an antibody, or antigen-binding fragment thereof, that binds to the extracellular domain of CXCL16 and blocks the binding of CXCL16 to CXCR6;
- and (ii) a composition comprising an immunosuppressive agent that inhibits activation of T cells and/or B cells, wherein the immunosuppressive agent is not an antibody, or antigen-binding fragment thereof, that binds CXCR6 or CXCL16, such that hypersensitivity to the antigen is reduced.
Dependencies are inferred from the claim text.