emactuzumab emactuzumab emactuzumab (rg-7155) is a humanized monoclonal antibody directed against colony stimulating factor 1 receptor (csf-1r) expressed on macrophages and has demonstrated a profound antitumor effect through interference with the csf-1/csf-1r axis, along with a manageable safety profile in patients with diffuse-type tenosynovial giant cell tumors (d-tgct). emactuzumabemactuzumab light (purple) and heavy (orange) chains complexed with csf-1r (green)monoclonal antibodytypewhole antibodysourcehumanized (from mouse)targetcsf1rclinical dataother namesrg7155, ro5509554routes ofadministrationintravenous infusionatc codenonepharmacokinetic dataelimination half-life1.5 - 9 daysidentifierscas number1448221-67-7drugbankdb14905unii6fy6ei1x8rkeggd11234chemical and physical dataformulac6398h9908n1704o2020s44molar mass144430.19 g·mol−1 history this drug was originally developed by roche/genentech. in august 2020, celleron therapeutics signed a deal to acquire an exclusive worldwide license for the asset. in november 2020, celleron therapeutics incorporated a subsidiary, synox therapeutics, to focus on the development, registration, and commercialisation of emactuzumab mechanism of action emactuzumab is a humanized monoclonal antibody directed against the tyrosine kinase receptor colony stimulating factor 1 receptor (csf1r; csf-1r; cd115), also known as macrophage colony-stimulating factor receptor (m-csfr), with potential antineoplastic and immunomodulating activities. upon administration, emactuzumab binds to csf1r expressed on macrophages and inhibits the binding of colony-stimulating factor-1 (csf-1) to csf1r. this prevents csf1r activation and csf1r-mediated signaling in these cells, which blocks the production of inflammatory mediators by macrophages and reduces inflammation. by blocking both the activity of csf1r-dependent tumor-associated macrophages (tams) and the recruitment of tams to the tumor microenvironment, emactuzumab enhances t-cell infiltration and antitumor t-cell immune responses, which inhibits the proliferation of tumor cells. tams play key roles in immune suppression and promoting inflammation, tumor cell proliferation and survival. clinical efficacy in a phase ib clinical study, biopsies were taken from tgct subjects before and on emactuzumab treatment, and immunohistochemistry was performed with antibodies against cd68/cd163 (biomarkers for tams) and csf-1r. altogether, 36 patients (57%) had evaluable paired tumour biopsy samples (taken at baseline and on treatment at four weeks, after two cycles of emactuzumab at doses of 900 – 2000 mg). a significant reduction of >50% of cd68/cd163-positive macrophages and csf1r-positive macrophages was seen in 22 patients (61%), showing that the neutralisation of csf-1r by emactuzumab resulted in the concomitant depletion of tams. in the efficacy cohort, 45 of 63 patients (71%) had a best overall response of complete response or partial response (pr) and the disease control rate was 98% (62 of 63 patients). none of the patients were assessed with progressive disease at the time of treatment discontinuation, although the majority of patients (39 patients ) only received a limited number of four or five treatment cycles. after one- and two-year follow-up mri, 19/27 patients (70%) and 9/14 patients (64%), respectively, were still in response at these time points.