axatilimab

A humanized immunoglobulin (Ig) G4 monoclonal antibody directed against colony-stimulating factor 1 receptor (CSF-1R; CSF1R; macrophage-CSFR; M-CSFR; CD115; c-fms), with potential antineoplastic activity and anti-inflammatory, immunomodulating and anti-fibrotic activities. Upon intravenous administration, axatilimab binds to the ligand binding domain of CSF-1R expressed on monocytes and macrophages, thereby preventing binding and consequent activation by its natural ligands, interleukin-34 (IL-34) and colony-stimulating factor 1 (CSF-1). Inhibition of CSF-1R activation and CSF1R-mediated signaling may reduce the levels of these circulating pro-inflammatory and pro-fibrotic monocytes and monocyte-derived macrophages. This prevents the secretion of a variety of pro-inflammatory cytokines by monocytes and macrophages, reduces inflammation, and inhibits the tumor necrosis factor-beta (TGF-b) secretion by profibrotic (M2) macrophages. This inhibits the TGF-b-mediated development of fibrosis and may treat chronic graft-versus-host disease (cGVHD). In addition, by blocking CSF-1R activation and CSF-1R-mediated signaling in tumor-associated macrophages (TAMs), axatilimab may abrogate the TAMs-mediated immunosuppression in the tumor microenvironment (TME) and may enhance T-cell infiltration and antitumor T-cell immune responses. This may inhibit the proliferation of tumor cells. TAMs play key roles in immune suppression and promoting inflammation, tumor cell proliferation and survival. CSF-1R is a tyrosine protein kinase that plays an essential role in the regulation, proliferation, survival and differentiation of tissue macrophages as well as TAMs.