| Background | Lacnotuzumab, as known as MCS110, is a novel, high-affinity, humanized, anti-CSF-1 monoclonal antibody that prevents CSF-1 from activating the CSF-1R. The drug is being developed by Novartis Europharm Limited. On 15 October 2014, orphan designation (EU/3/14/1350) was granted by the European Commission to Novartis for recombinant human monoclonal antibody of the IgG1 kappa class against human macrophage colony-stimulating factor for the treatment of tenosynovial giant cell tumor, localized and diffuse type. They conducted a phase 1 study to assess the safety and tolerability of administering single ascending doses and repeat doses of lacnotuzumab to healthy volunteers, and to examine the pharmacokinetics (PK), pharmacodynamics (PD), and mechanistic properties of lacnotuzumab. Nonclinical investigations of the mechanism of action of lacnotuzumab were also performed to explain the observed adverse events (AEs) profile associated with CSF-1 pathway inhibition. Lacnotuzumab was generally well tolerated. The majority of AEs were low grade, no unexpected or novel AEs were observed, and there were no discontinuations for AEs. Lacnotuzumab also showed dose-dependent, on-target effects on multiple downstream biomarkers. Preclinical investigations of the CK elevation and periorbital swelling observed after lacnotuzumab administration suggest that these are reversible, nonpathological events linked to inhibition of the CSF-1 pathway. These data support further evaluation of lacnotuzumab in clinical studies.
• Potent BRD4 inhibitor suppresses cancer cell-macrophage interaction., PMID:32286255
• p53 Gain-of-Function Mutation Induces Metastasis via BRD4-Dependent CSF-1 Expression., PMID:37676642
• Pexidartinib: First Approval., PMID:31602563
• Human Tumor-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets., PMID:30930117
• CSF1/CSF1R Signaling Inhibitor Pexidartinib (PLX3397) Reprograms Tumor-Associated Macrophages and Stimulates T-cell Infiltration in the Sarcoma Microenvironment., PMID:34088832
• Osteoclast Differentiation Assay., PMID:30378050
• Colony stimulating factor-1 receptor drives glomerular parietal epithelial cell activation in focal segmental glomerulosclerosis., PMID:38428734
• Elevated expression of the colony-stimulating factor 1 (CSF1) induces prostatic intraepithelial neoplasia dependent of epithelial-Gp130., PMID:34999736
• Therapeutic advances in Tenosynovial giant cell Tumor: Targeting the CSF1/CSF1R axis., PMID:40020639
• Catechism (Quiz 13)., PMID:34341297
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