# US 9,872,905 B2 · Modulation of NK cell antigen specific effector activity by modulation of CXCR6 (CD186) > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,872,905 B2 - Document ID: US9872905B2 - Status: Granted - Kind: B2 - Application number: 13/512,754 - Filed: 2010-12-01 - Published: 2013-04-25 - Granted: 2018-01-23 - Earliest claimed: 2009-12-01 - Assignees: President and Fellows of Harvard College - Applicants: Ulrich Von Andrian; Silke Paust - Inventors: Ulrich Von Andrian; Silke Paust - Web page: https://patentgrep.com/patent/US9872905B2 ## CPC - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 38/177: {Receptors; Cell surface antigens; Cell surface determinants} - A61K 38/195: {Chemokines, e.g. RANTES} - A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines} - C07K 16/2866: {against receptors for cytokines, lymphokines, interferons} - C12Q 1/025: {for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics (antimicrobial activity C12Q1/18)} - A61K 2039/505: {comprising antibodies} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES ## 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. ## Claims ### Claim 1 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. ### Claim 2 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. ### Claim 3 (depends on 1, 2) The method of claim 1 or 2, wherein the subject has delayed-type hypersensitivity to an antigen or is at risk for developing delayed-type hypersensitivity to an antigen. ### Claim 4 (depends on 3) The method of claim 3, wherein the antigen is a hapten. ### Claim 5 (depends on 3) The method of claim 3, wherein the step of administering is performed after secondary exposure to the antigen and prior to the onset of a delayed-type hypersensitivity reaction. ### Claim 6 (depends on 3) The method of claim 3, wherein the step of administering is performed after secondary exposure to the antigen and after onset of a delayed-type hypersensitivity reaction. ### Claim 7 (depends on 3) The method of claim 3, wherein the step of administering is performed prior to secondary exposure to the antigen. ### Claim 8 (depends on 1, 2) The method of claim 1 or 2, wherein the subject suffers from an occupational allergy. ### Claim 9 (depends on 1, 2) The method of claim 1 or 2, wherein the step of administering is performed more than once. ### Claim 10 (depends on 1, 2) The method of claim 1 or 2, further comprising administration of an immunosuppressive agent that inhibits activation of T cells and/or B cells. ### Claim 11 (depends on 10) The method of claim 10, wherein the subject does not respond adequately to said immunosuppressive agent when administered alone. ### Claim 12 (depends on 1, 2) The method of claim 1 or 2, wherein the subject has or is at risk for developing a deleterious immune response to an infectious agent. ### Claim 13 (depends on 12) The method of claim 12, wherein the infectious agent is a virus. ### Claim 14 (depends on 12) The method of claim 12, wherein the infectious agent is a bacteria. ### Claim 15 (depends on 12) The method of claim 12, wherein the infectious agent is a virus selected from the group consisting of: hepatitis B virus, influenza virus, hepatitis C virus, varicella zoster, herpes virus, HIVI and HIV2. ### Claim 16 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. ### Claim 17 (depends on 16) The method of claim 16, wherein the delayed-type hypersensitivity is due to an occupational allergy.