Compositions and methods for modulating lymphocyte activity
AssigneeWashington University in St. Louis
InventorsJames P. Allison, Kenneth P. Murphy, Norihiko Watanabe, Theresa L. Murphy, Jianfei Yang, Xingxing Zang
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Abstract
The present invention provides a novel lymphocyte inhibitory receptor termed BTLA which is expressed on both T and B cells, and identifies B7 family member B7x as interacting with BTLA to attenuate lymphocyte activity. Methods and compositions for modulating BTLA-mediated negative signaling and interfering with the interaction of BTLA and B7x for therapeutic, diagnostic and research purposes are also provided.
Claims87
A method for modulating lymphocyte activity, comprising contacting a BTLA-positive lymphocyte with a bioactive agent capable of modulating BTLA-mediated signaling in an amount effective to modulate at least one lymphocyte activity.
A method for modulating the interaction of a BTLA-positive lymphocyte with a B7x-positive cell, comprising contacting a BTLA-positive lymphocyte with a bioactive agent capable of modulating BTLA-mediated signaling in an amount effective to modulate at least one lymphocyte activity.
A bioactive agent for modulating lymphocyte activity, wherein said bioactive agent comprises an antagonist of BTLA-mediated signaling which is capable of inhibiting the attenuation of lymphocyte activity mediated by BTLA signaling.
A bioactive agent for modulating lymphocyte activity, wherein said bioactive agent comprises an agonist of BTLA-mediated signaling, and said modulation decreases lymphocyte activity.
A method for treating cancer in a patient having B7x-positive tumor cells comprising administering to the patient an antagonist of BTLA-mediated signaling, wherein said administration is effective to increase the host immune response against said B7x-positive tumor cell.
A method for treating a patient having an autoimmune disease characterized by the presence of autoreactive BTLA-positive lymphocytes, comprising administering to the patient an agonist of BTLA-mediated signaling, wherein said administration is effective to inhibit an autoreactive immune response against non-lymphoid non-tumor host cells expressing B7x.
A recombinant BTLA nucleic acid, comprising a nucleotide sequence having at least about 70% identity to the nucleotide sequence set forth in SEQ ID NO:7 or 9.
A recombinant BTLA nucleic acid, which will hybridize under moderately or highly stringent conditions to a nucleic acid comprising the nucleotide sequence set forth in SEQ ID NO:7 or 9 or the complement thereof.
A recombinant BTLA nucleic acid, encoding a BTLA protein comprising the amino acid sequence set forth in SEQ ID NO:8 or 10.
An isolated BTLA protein, comprising an amino acid sequence having at least about 70% identity to the amino acid sequence set forth in SEQ ID NO:8 or 10.
Dependencies are inferred from the claim text.