High Efficiency Anionic Nanoparticle Encapsulation of Oncolytic Viruses for Metastatic Cancer Therapy
Ralph Feuer, Ph.D.
Andrew C. Kummel, Ph.D.
The encapsulation of oncolytic virus TAV-255 in anionic Lecithin liposomes to increase its therapeutic efficacy will be investigated in an animal model along with the effect of the encapsulation on the immune response. 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. OVs are promising agents because of their capacity to self-replicate. Although they are effective when administered locally, the utility of OVs to treat metastatic cancer is limited by 1) the lack of expression of CAR cell surface receptors necessary for cell entry, 2) rapid clearance by the reticuloendothelial (RE) system in the liver, and 3) neutralization by antibodies. An encapsuation approach of OVs in anionic liposomes has been tailored with an effort to mask the virus from the immune system, increase its circulation time in the bloodstream, and allow OVs to reach the tumor site without non-specific uptake in other organs. There are two aims: Aim 1: Effect of immune response after the administration of virus. An animal study in healthy mice will be utilized to examine the effect of the innate and adaptive immune response after intravenous administration of encapsulated adenovirus in lecithin liposomes. A cytokine release study will be used to study the innate immune response, and neutralizing antibodies will be measured to investigate the adaptive immune response in blood samples. Aim 2: Anti-tumoral effects of TAV-255 in vivo. An in vivo investigation in tumor-bearing mice will be used to examine the anti-tumoral effects of encapsulated vs. non-encapsulated oncolytic virus after repeated systemic delivery. The study is designed to determine the anti-tumoral effects of TAV-255 using lecithin liposomes as a carrier to subcutaneous tumor implants in an immunocompetent cancer mouse model. The anti-tumoral effects of the combination of the liposome with adenoviral vectors will be determined. Excised tumors will be inspected for signs of histopathology, immune infiltration, and apoptotic activity. A novel, low cost therapy for metastatic cancer has the potential to reduce the impact of medically underserved populations having higher rates of many types of metastatic cancer.
Project Period: 5/10/2013 – 8/31/2013