Therapeutic peptide for hepatocellular carcinoma

Therapeutic peptide for hepatocellular carcinomaNiranjan BPandeyPh DPIAleksander SPopelPh DCo IJordan JGreen Ph DCo I Phuoc TTran M DPh DPI of subcontract Project SummaryThere are very limited options currently available for the treatment of hepatocellular carcinomaHCCthe most common type of liver cancerHCClike most forms of canceris dependent on angiogenesisthe growth of blood vesselsThese and other tumors use VEGF and Angto induce angiogenesisThe tumor also uses these factors to suppress the immune systemAnti VEGF agents inhibit angiogenesis and also allow some activation of the immune system but they induce hypoxia which is itself immune suppressiveWe have identified a peptide that simultaneously inhibits VEGF and activates Tiethe receptor for AngThis peptideAXTthus inhibits angiogenesis but promotes normalization of the remaining vasculature thus avoiding hypoxia and immune suppressionIn addition by inhibiting VEGF and activating TieAXTcould make the immune system more anti tumorigenic by allowing more dendritic cell maturationmore T cell proliferation and infiltration into the tumorand reduced number of regulatory T cells in the tumorCheckpoint inhibitors are promising therapies for cancer but they have challenges with toxicity and also they only work in a minority of patientsThe efficacy of these immunotherapies is minimized by an immune system kept suppressed by tumorsWe hypothesize that AXTwill enhance the efficacy of an anti PDantibody by making the immune system more anti tumorigenicHere we propose to determine if the combination of AXTand anti PDantibody increase survival of mice with lethalautochthonous HCC tumors compared to anti PDor AXTaloneWe will also test for evidence of immune system activation by AXTFinally we propose studies to facilitate translation of AXTinto the clinicSuccessful completion of the project will result in the creation of a powerfulnew therapeutic for the treatment of hepatocellular carcinoma and also help AsclepiX Therapeutics reach a critical milestone Project NarrativeTumors are versatile and one of the ways they survive is by suppressing the immune systemImmunotherapies are promising for treating hepatocellular carcinoma but they only help a minority of patientsIn this project we propose to test a combination of our promisingimmunoactivatingmultifunctional therapeutic peptide together with a checkpoint inhibitor to enhance survival of mice with lethal hepatocellular carcinoma tumorsWe also propose studies that will facilitate the translation of our peptide into the clinic