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Background: The characteristic feature of immune cytopenias involves the process of extravascular phagocytosis, wherein macrophages in the spleen and/or liver engage in the destruction of blood cells that have been opsonized by auto‐ or alloantibodies. Therefore, new treatments that prevent phagocytosis will be advantageous, especially for short‐term usage along with alternative options. Study Design and Methods: KB‐208, a small molecule drug, previously shown to be efficacious for the in vitro inhibition of phagocytosis was synthesized. A passive antibody mouse model of immune thrombocytopenia (ITP) was used. Three different mouse strains (BALB/c, C57BL/6, CD1) were used to determine the efficacy of KB‐208 compared with IVIG to ameliorate the ITP. Toxicity was investigated after 60‐day chronic administration of KB‐208 by a biochemistry panel, gross necroscopy and histopathology. Results: KB‐208 showed similar efficacy to ameliorate the thrombocytopenia compared with IVIG in all three mouse strains. This small molecule drug was effective at 1 mg/kg in ameliorating ITP, in comparison with IVIG at 1000–2500 mg/kg. KB‐208 did not affect other blood parameters or elevate serum biochemistry markers of toxicity nor were any abnormal histopathological findings found. Conclusion: KB‐208 is similar to IVIG for the amelioration of ITP in multiple mouse strains. Chronic administration of KB‐208 for 60 days did not demonstrate in vivo toxicity. These findings indicate that KB‐208 is efficacious, without significant in vivo toxicities in mice, and is a potential small molecule candidate for further evaluation to be used in the treatment of ITP and possibly all immune cytopenias where phagocytosis is responsible for the pathophysiology. [ABSTRACT FROM AUTHOR]

Background and Aims: Hepatocellular carcinoma (HCC) is a highly aggressive tumor with limited treatment options and high mortality. Senecavirus A (SVA) has shown potential in selectively targeting tumors while sparing healthy tissues. This study aimed to investigate the effects of SVA on HCC cells in vitro and in vivo and to elucidate its mechanisms of action., Methods: The cell counting kit-8 assay and colony formation assay were conducted to examine cell proliferation. Flow cytometry and nuclear staining were employed to analyze cell cycle distribution and apoptosis occurrence. A subcutaneous tumor xenograft HCC mouse model was created in vivo using HepG2 cells, and Ki67 expression in the tumor tissues was assessed. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay and hematoxylin and eosin staining were employed to evaluate HCC apoptosis and the toxicity of SVA on mouse organs., Results: In vitro , SVA effectively suppressed the growth of tumor cells by inducing apoptosis and cell cycle arrest. However, it did not have a notable effect on normal hepatocytes (MIHA cells). In an in vivo setting, SVA effectively suppressed the growth of HCC in a mouse model. SVA treatment resulted in a significant decrease in Ki67 expression and an increase in apoptosis of tumor cells. No notable histopathological alterations were observed in the organs of mice during SVA administration., Conclusions: SVA inhibits the growth of HCC cells by inducing cell cycle arrest and apoptosis. It does not cause any noticeable toxicity to vital organs., Competing Interests: LC has been an Associate Editor of the Journal of Clinical and Translational Hepatology since 2013. The other authors have no conflicts of interest related to this publication., (© 2024 Authors.)