HIGH AFFINITY PD-1 AGENTS AND METHODS OF USE

摘要

High affinity PD-1 mimic polypeptides are provided, which (i) comprise at least one amino acid change relative to a wild-type PD-1 protein; and (ii) have an increased affinity for PD-L1 relative to the wild-type protein. Compositions and methods are provided for modulating the activity of immune cells in a mammal by administering a therapeutic dose of a pharmaceutical composition comprising a high affinity PD-1 mimic polypeptide, which blocks the physiological binding interaction between PD-1 and its ligand PD-L1 and/or PD-L2.

主权项

1. A high affinity PD-1 mimic polypeptide, wherein the polypeptide is a variant of a wild-type PD1 sequence, which:
(a) lacks the PD-1 transmembrane domain, and (b) comprises one or more amino acid changes relative to a corresponding sequence of the wild type PD-1 polypeptide, wherein the one or more amino acid changes increases the affinity of the polypeptide for PD-L1 as compared to the affinity for PD-L1 of the corresponding wild type PD-1 polypeptide.