Modified AXL peptides and their use in the inhibition of AXL signaling in anti-metastatic therapy

摘要

A GAS6 inhibitor, wherein the inhibitor is a soluble AXL variant polypeptide, wherein said soluble AXL variant polypeptide: is a fusion protein; lacks the AXL transmembrane domain; it lacks a functional fibronectin (FN) domain, has one or more of an Ig1 domain and, optionally, one or more of an Ig2 domain; it comprises a set of amino acid substitutions at positions, in relation to SEQ ID NO: 1: G32, A72, D87, V92 and G127; or in positions G32, D87, V92 and G127; comprises an Fc domain bound to the soluble AXL variant polypeptide by a spacer comprising one or more (GLY) 4SER units (SEQ ID NO: 10); and has a higher affinity for binding to GAS6 compared to wild-type AXL (SEQ ID NO: 1).