Fig. 5.
TAX2: binding, pharmacokinetics, and biodistribution studies. a Schematic diagram illustrating the mechanism of action of TAX2, which binds the carboxy-terminal domain of TSP-1, selectively inhibiting TSP-1/CD47 interaction. b Graph displaying the dose–response curve for the binding between TAX2 and labeled rhTSP-1 (10−8 M) as assessed by microscale thermophoresis. c Evaluation of TAX2 biodistribution in healthy C57BL/6 J mice using FMT after IV administration of a dose range of TAX2-Cy5 (1, 5, 10, or 20 mg/kg, 2–6 mice/group). Fluorescence quantification was performed on collected tissues at T0. The middle part of panel c presents the TSP-1 gene (THBS1) expression in various human tissues obtained from the Human Protein Atlas database, combining datasets from HPA, GTEx, and FANTOM5 as of April 2024. The table (lower part of panel) presents fluorescent quantification on plasma collected at T0. d Assessment of TAX2-Cy5 biodistribution (administered IV at a 10 mg/kg BW dose) in mice bearing ID8 Trp53−/− Brca2.−/− ovarian carcinoma cells injected either subcutaneously (SC) or intraperitoneally (IP). Fluorescence quantification using FMT was conducted on live mice after 24 h (bottom panel). Subsequently, subcutaneous tumors (black bar, SC model), peritoneal tumor masses, and metastatic nodules (pink and brown bars, respectively, IP model) were excised post euthanasia and then imaged for TAX2-Cy5 quantification. Necropsy (bottom panel, right image) reveals metastases in the omentum (highlighted by white arrows)
