Service Project #4: Therapeutic peptide for hepatocellular carcinoma
Collaborating Investigator: Niranjan Pandey
Affiliation: AsclepiX Therapeutics
Funding: NIH 1R43CA232947
Project Period: 09/01/18-08/31/19
There are very limited options currently available for the treatment of hepatocellular carcinoma (HCC), the most common type of liver cancer. HCC, like most forms of cancer, is dependent on angiogenesis, the growth of blood vessels. These and other tumors use VEGF and Ang2 to induce angiogenesis. The tumor also uses these factors to suppress the immune system. Anti-VEGF agents inhibit angiogenesis and also allow some activation of the immune system but they induce hypoxia which is itself immune suppressive. We have identified a peptide that simultaneously inhibits VEGF and activates Tie2, the receptor for Ang2. This peptide, AXT201, thus inhibits angiogenesis but promotes normalization of the remaining vasculature thus avoiding hypoxia and immune suppression. In addition, by inhibiting VEGF and activating Tie2, AXT201 could make the immune system more anti-tumorigenic by allowing more dendritic cell maturation, more T-cell proliferation and infiltration into the tumor, and reduced number of regulatory T cells in the tumor. We hypothesize that AXT201 will enhance the efficacy of an anti-PD-1 antibody by making the immune system more anti-tumorigenic. Need for TR&D Technology: The goal of SP#4 is the development of biomimetic peptide-based therapeutic that can regulate vessel growth and stimulate the immune system against tumors. Nanoimmunomaterials (NIM)s developed as part of TR&D2 will be utilized for construction of nanoparticles (push) that deliver peptides to tumors. By enabling control of the size, shape, presentation, and release from these particles, the company’s goals can be better achieved than with the commercially available particle technologies that are currently on the market. This SP demonstrates how the NIM technology is of use to industry and NIM technology will be disseminated (push) to both academia and industry.
Specific Aim: AXT201 activates the Tie2 pathway, which has been recently shown to strongly promote an immune activating tumor microenvironment. Here we propose studies to enhance the efficacy of AXT201 and also explore the feasibility of delivering it in a controlled release manner over time.