Development of a filamentous plant virus for chemo-immunotherapy delivery

K.L. Lee, N.F. Steinmetz
Case Western Reserve University,
United States

Keywords: plant viral nanoparticles, potato virus x, doxorubicin, chemo-immunotherapy

Summary:

Each year, one million new cases of cancer are diagnosed in the US, with the most aggressive types commonly being treated with chemotherapy. However, these therapies can cause many side effects when administered systemically and are often not effective for long-term treatment due to the development of resistant cells over time. Recent data suggest that combining chemotherapy with immunotherapy can improve therapeutic efficacy. Nanoparticles can be used to deliver multiple payloads simultaneously to improve overall efficacy, while also decreasing side effects associated with delivery of free therapeutics. Specifically, plant viral nanoparticles are being investigated as carrier systems to deliver therapies to specific cells and tissues. Viral nanoparticles (VNPs) have symmetrical structures that are amenable to chemical and genetic engineering, and can be produced in high yields in plants. Additionally, VNPs from plants are biocompatible, biodegradable, and non-infectious in mammals, while also having tunable immunogenicity. We have previously shown that a virus-like particle derived from the icosahedral plant virus cowpea mosaic virus can reduce tumor burden and metastatic sites in multiple models of murine cancer. Here, we investigate the use of Potato virus X (PVX), a filamentous virus for a chemo-immunotherapy. PVX measures 515 x 13 nm and is comprised of 1270 identical coat proteins, each containing a solvent-exposed lysine residue, which is available for chemical modification. We have previously shown that PVX can be modified with targeting ligands to for specific uptake in cancer cells. These filaments can also be loaded with doxorubicin (DOX), a chemotherapy commonly used for cancer treatment, directly to PVX filaments due to hydrophobic interactions. Here, we investigate cell killing of DOX-loaded filaments in a panel of cancer cell lines, as well as the therapeutic efficacy of PVX filaments in a murine model of melanoma.