AVS 60th International Symposium and Exhibition | |
Biomaterial Interfaces | Wednesday Sessions |
Session BI-WeM |
Session: | Cell-Surface Interactions |
Presenter: | N. Mendez, University of California San Diego |
Authors: | N. Mendez, University of California San Diego V. Herrera, University of California San Diego F. Hedjran, University of California San Diego S.L. Blair, University of California San Diego T. Reid, University of California San Diego W.C. Trogler, University of California San Diego A.C. Kummel, University of California San Diego |
Correspondent: | Click to Email |
Several treatment modalities such as surgery, radiation, and chemotherapy are effective for cancer treatment however also face several limitations. Alternatively, oncolytic viruses (OVs) can target multiple mechanisms of action while at the same time exploit validated genetic pathways known to be disregulated in many cancers. In particular, the oncolytic virus TAV-255 has shown viral replication attenuation in normal cells while retaining cytolytic activity in tumor cells by taking advantage of defects in the p53-tumor suppressor pathway. Despite its several advantages, the utility of OVs for cancer therapy is limited by 1) neutralization by antibodies mediated by the immune system, 2) rapid clearance by the reticuloendothelial (RE) system in the liver, and 3) the lack of expression of surface receptors (CAR) in certain cancers necessary for OV transduction. Oncolytic viruses are promising agents to combine with nanoparticle delivery approaches because of the capacity for self-replication of the virus. In systemic delivery, targeting with nanoparticles may focus the viral load to the primary tumor cells as well as metastatic tumors to insure a productive initial infection. A non-toxic liposomal delivery system has been developed for delivery of the virus to tumor cells. Further, with the aim to overcome an immune response and to enhance its potential use to treat primary and metastatic tumors, an encapsulation method involving an anionic non-toxic liposome has been prepared by self-assembly of Lecithin around the viral capsid. The developed method has shown that encapsulated viruses retain their ability to infect cancer cells. Furthermore, an immunoprecipitation (IP) technique has shown to be a fast and effective method to extract non-encapsulated viruses and homogenize the liposomes remaining in solution. Extracting non-encapsulated viruses from solution may prevent an adverse immune response when used in an in vivo model and may enhance treatment for multiple administrations.