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 programmed cell death 1 (PD-1) mimic polypeptide, comprising an amino acid sequence that is a variant of a human wild-type PD-1 ectodomain sequence, wherein the high affinity PD-1 mimic polypeptide:
(a) lacks a wild-type PD-1 transmembrane domain, (b) comprises an amino acid sequence having 85% or more sequence identity to the amino acid sequence set forth in any of SEQ ID NOs: 2-25 and 39-46, and (c) relative to the amino sequence set forth in SEQ ID NO: 2, comprises one or more amino acid changes that cause an increased affinity for human and/or mouse programmed cell death 1 ligand 1 (PD-L1).