Beijing Shenogen Pharma Group Ltd. Disclosed the New Findings Related to Icaritin treatment induced Immunomodulation in HCC Tumor Microenvironment

Published:2021-1-6 10:23:09 Views:473

Recently, the internationally renowned European Journal of Immunology published an online article "Icaritin inhibits PD-L1 expression by targeting protein IκB Kinase α" (DOI: 10.1002 /eji. 202048905) that shared the new research data showing the direct evidence of icaritin-protein interaction in immune modulation, which revealed the underlying mechanism of icaritin antitumor effect is through immune regulation. Icaritin is the active constituent of SNG162, one of the leading research pipelines of Beijing Shenogen Pharma Group Ltd. that is currently being evaluated in phase III clinical trials (NCT03236636 and NCT03236649) to treat advanced HBV-related hepatocellular carcinoma (HCC).

The novel small molecule icaritin was extracted from traditional Chinese herb Epimedium genuscurrently and has been developed as a small molecule immune-modulating agent to treat advanced liver cancer. Based on recent years of studies, the biological research team of Shenogen Pharma Group found that protein IκB Kinase α (IKKα) is one of the binding protein targets of icaritin. Functionally, icaritin inhibited the NF-κB signaling pathway by blocking IKK protein complex formation, which impeded the nuclear translocation of NF-κB/p65, and subsequently down-regulated PD-L1 expression. The new research publication reported that the combined treatment of icaritin with antibodies against immune-checkpoint protein such as α-PD-1 demonstrated better anticancer efficacy than any single-agent treatment in vivo. This study clearly revealed that icaritin treatment induced anticancer activities are mediated, at least in part, via impairing the biological functions of IKKα and the associated signaling pathways. The disclosed data and molecular mechanisms of icaritin has enriched the biological understanding of anti-inflammatory and immune regulating pathways through NF-κB/MyD88 and IKK protein complex in liver cancer. These findings provided supporting evidence for clinical development of icaritin as small molecule-based immune modulator that have a great potential to combine with immune checkpoint blockade agents in treating advanced cancer patients and to improve anti cancer efficacy and safety profiles.