MULTISPECIFIC HIGH AFFINITY PD-1 AGENTS AND METHODS OF USE

摘要

Multispecific high affinity PD-1 mimic polypeptides are provided, which comprise: (a) a first region comprising an amino acid sequence of a high affinity PD-1 mimic polypeptide that is a variant of a wild-type PD1 sequence; and (b) a second region comprising an amino acid sequence of a high affinity SIRP-alpha variant that specifically binds to CD47, where the high affinity SIRP-alpha variant is CV1. 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 subject multispecific high affinity PD-1 mimic polypeptide, which blocks the physiological binding interaction between PD-1 and its ligand PD-L1 and/or PD-L2.