Oncolytic viruses can exploit validated genetic pathways known to be deregulated in many cancers and are directly cytolytic.  Viral gene therapy holds great promise due to the approach which takes advantage of the virus' ability to replicate within cancer cells to levels that are many logs higher than the input dose, lyse the infected cell and subsequently spread to adjacent cells.  In particular, the oncolytic adenovirus 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 neutralization by antibodies mediated by the immune system, rapid clearance by the reticuloendothelial (RE) system in the liver, and the lack of expression of surface receptors (CAR) in certain cancers necessary for OV transduction. With the aim to overcome an immune response and to enhance its potential use to treat primary and metastatic tumors, a method for liposomal encapsulation of adenovirus has been developed. The encapsulation of Adenovirus in 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 and serum stability. PEGylated liposomes have the potential to increase the circulation time of Adenovirus after systemic delivery which can enhance the efficacy of OV therapy. 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.

Designing a nontoxic liposomal delivery system to enhance oncolytic viral therapy

247th National Meeting (2014)

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