Clinical evaluation of colony-stimulating factor 1 receptor inhibitors. (April 2021)

• Record Type: Journal Article
• Authors: Ordentlich, Peter
• Is Part Of: Seminars in immunology. Volume 54(2021)
• Publication Date: 2021-04
• Subjects: AE adverse event -- ALT alanine aminotransferase -- AST aspartate aminotransferase -- bid twice a day -- c-KIT tyrosine-protein kinase KIT -- CCL2 C-C motif chemokine ligand 2 -- cGVHD chronic graft-versus-host disease -- CLE cutaneous lupus erythematous -- CPK creatine phosphokinase -- CRC colorectal cancer -- CSF1 colony-stimulating factor 1 -- CSF1R colony-stimulating factor 1 receptor -- CSF1Ri colony-stimulating factor 1 receptor inhibitors -- CTX-1 C-terminal telopeptide -- DLT dose-limiting toxicity -- DOR duration of response -- dt-TGCT diffuse-type tenosynovial giant cell tumor -- ECM extracellular matrix -- FLT3 Fms-related receptor tyrosine kinase 3 -- GAG glycosaminoglycans -- GBM glioblastoma multiforme -- GGT gamma glutamyltransferase -- GIST gastrointestinal stromal tumor -- HA hyaluronic acid -- HNSCC head and neck squamous cell carcinoma -- IL-34 interleukin 34 -- IPF idiopathic pulmonary fibrosis -- irRECIST immune-related response evaluation criteria in solid tumors -- LDH lactate dehydrogenase -- mAb monoclonal antibody -- M-CSF macrophage colony-stimulating factor -- MMP matrix metalloprotease -- MTD maximum tolerated dose -- mTOR mammalian target of rapamycin -- NSCLC non-small cell lung cancer -- NTX N-terminal telopeptide -- OBD optimal biological dose -- ORR overall response rate -- PD pharmacodynamic -- PD-1 programmed cell death 1 -- PD-L1 programmed death ligand 1 -- PDAC pancreatic ductal adenocarcinoma -- PDGFRα/β platelet-derived growth factor receptor α/β -- PK pharmacokinetic -- PR partial response -- RA rheumatoid arthritis -- RANO response assessment in neuro-oncology -- RECIST v1.1 response evaluation criteria in solid tumors, version 1.1 -- RP2D recommended phase 2 dose -- SD stable disease -- TAM tumor-associated macrophage -- TEAE treatment-emergent adverse event -- TGCT tenosynovial giant cell tumor -- TGFβ transforming growth factor β -- TME tumor microenvironment -- TRAE treatment-related adverse event -- TVS tumor volume score; Targeted therapy -- CSF1 inhibitors -- CSF1R inhibitors -- Receptor tyrosine kinase -- Solid tumours -- Graft-versus-host disease; Immunology -- Periodicals; Allergy and Immunology -- Periodicals; Immunity -- Periodicals; Immunologie -- Périodiques; Electronic journals; 616.079
• DOI: 10.1016/j.smim.2021.101514
• Languages: English
• ISSNs: 1044-5323

Abstract

Abstract: Signaling through colony-stimulating factor 1 receptor (CSF1R) regulates the development, differentiation, and activation of mononuclear phagocytic cells. Inhibition of this pathway provides an opportunity for therapeutic intervention in diseases in which these cells play a pathogenic role, including cancers, inflammation, fibrosis, and others. Multiple monoclonal antibodies and small molecule inhibitors targeting CSF1R or its known ligands CSF1 and IL-34 have been clinically tested and are generally well tolerated with side effects associated with on-target macrophage inhibition or depletion. To date, clinical activity of CSF1R inhibitors has been primarily observed in diffuse-type tenosynovial giant cell tumors, a disease characterized by genetic alterations in CSF1 leading to dysregulated CSF1R signaling. Expanded development into novel indications such as chronic graft vs host disease may provide new opportunities to further explore areas where a role for CSF1R dependent monocytes and macrophages has been established. This review presents key findings from the clinical development of 12 CSF1/CSF1R targeted therapies as monotherapy or in combination with immune checkpoint inhibitors and chemotherapy.