High affinity pd-1 agents and methods of use
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsAaron Michael Ring, Andrew Kruse, Aashish Manglik, Irving L. Weissman, Roy Louis Maute, Melissa N. McCracken, Sydney Gordon
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Abstract
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.
Claims15
A high affinity PD-1 mimic polypeptide comprising an amino acid sequence having 85% or more sequence identity to the amino acid sequence as set forth in SEQ ID NO:
- 2 and lacking a wild-type PD-1 transmembrane domain, wherein relative to the human wild-type PD-1 polypeptide as set forth in SEQ ID NO:
- 2, the high affinity PD-1 mimic polypeptide comprises one or more amino acid changes that increase the affinity of the high affinity PD-1 mimic polypeptide for PD-L1 as compared to the affinity for PD-L1 of the human wild type PD-1 polypeptide, the one or more amino acid changes located at an amino acid position selected from:
- V39, L40, N41, Y43, R44, M45, S48, N49, Q50, T51, D52, K53, A56, Q63, G65, Q66, V72, H82, M83, R90, Y96, L97, A 100, S102, L103, A104, P105, K106, and A107, and wherein the high affinity PD-1 mimic polypeptide comprises a fusion partner.
Dependencies are inferred from the claim text.