PD-1 ANTAGONISTS AND METHODS OF USE THEREOF
First Claim
1. A method of modulating an immune response comprising administering an effective amount a PD-1 antagonist to induce, augment, or enhance an immune response against a tumor, wherein the dose of the molecule, the timing of administration of the molecule and/or the affinity of the molecule allows for intermittent access of a ligand to the PD-1 receptor.
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Accused Products
Abstract
Compositions and methods for enhancing and/or prolonging the activation of T cells (i.e., increasing antigen-specific proliferation of T cells, enhancing cytokine production by T cells, stimulating differentiation ad effector functions of T cells and/or promoting T cell survival) or overcoming T cell exhaustion and/or anergy are provided. Suitable compositions include PD-1 receptor antagonists that bind to and block the endogenous PD-1 receptor without triggering inhibitory signals from PD-1, or bind to and block PD-1 receptor ligands and preventing them from interacting with PD-1 receptors. Methods for using the PD-1 receptor antagonists to enhance immune responses in subjects in need thereof are provided.
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Citations
30 Claims
- 1. A method of modulating an immune response comprising administering an effective amount a PD-1 antagonist to induce, augment, or enhance an immune response against a tumor, wherein the dose of the molecule, the timing of administration of the molecule and/or the affinity of the molecule allows for intermittent access of a ligand to the PD-1 receptor.
- 17. A composition comprising an effective amount of a PD-1 receptor antagonist to bind to a ligand of a PD-1 receptor in vivo and reduce or inhibit PD-1 receptor signal transduction.
- 24. A composition comprising an effective amount of a polypeptide to bind PD-1 in vivo without triggering signal transduction through PD-1.
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27. A fusion polypeptide comprising:
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a) a first fusion partner, and b) a second fusion partner, wherein the first fusion partner comprises a variant extracellular domain or fragment thereof of a ligand of PD-1 modified to bind PD-1 without triggering signal transduction through PD-1 and wherein the first fusion partner is fused directly to the second fusion partner, or optionally, is fused to a linker sequence that is fused to the second fusion partner. - View Dependent Claims (28, 29, 30)
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Specification