Anti-CSF1 polyclonal antibody

Pigmented villonodular synovitis (PVNS), alternatively known as diffuse-type tenosynovial giant cell tumor (D-TGCT), is a rare joint disease tumor affecting young adults. Standard management requires iterative surgery, which may significantly impact quality of life. The molecular hallmark is a chromosomal translocation resulting in the fusion of an isotype of collagen with colony-stimulating factor 1 (CSF1) by the tumor cell component. This leads to an overproduction of the cytokine and the recruitment of CSF1-receptor (CSF1R)-expressing macrophages, eventually forming a locally destructive proliferation. TGCT is therefore considered as a neoplastic proliferation, locally aggressive and very rarely metastatic. CSF1R inhibitors have the potential to inhibit this pathogenetic loop, and are currently under investigation in several clinical trials. These inhibitors include small molecules like imatinib, nilotinib and pexidartinib, and monoclonal antibodies such as emactuzumab, MCS-110 and FPA-008. Preliminary efficacy data suggests that these drugs have the potential to modify the current management of D-TGCT. As CSF1 is also implicated in protumoral macrophage polarization, CSF1R inhibitors are also tested in combination with other immunotherapies in a wide variety of solid tumors. This review aims to describe the future management of D-TGCT in the era of CSF1R inhibitors.

Introduction: Tenosynovial giant cell tumor (TGCT) is a benign clonal neoplastic proliferation arising from the synovium often causing pain, swelling, joint stiffness, and reduced quality of life. The optimal treatment strategy in patients with diffuse-type TGCT (dt-TGCT) is unclear. The purpose of this review is to describe recent advances in the knowledge of TGCT pathogenesis and potential therapeutic implications. Areas covered: Current treatment options for TGCT are discussed, including surgery and radiotherapy. Recent evidence that TGCT cells overexpress colony-stimulating factor 1 (CSF1), resulting in recruitment of CSF1 receptor (CSF1R) positive tumor-associated macrophage and contributing to tumor growth, has created new opportunities for systemic treatments of dt-TGCT. Results of clinical trials with CSF1R inhibitors are now available. These inhibitors include small molecules such as imatinib, nilotinib, pexidartinib, and monoclonal antibodies like emactuzumab, MCS110, and cabiralzumab. Expert opinion: TGCT impairs patients' quality of life significantly. The confirmation that the pathogenetic loop of TGCT can be inhibited through targeted agents could potentially change the therapeutic armamentarium for this condition.