Abstract 1816: Impact of 5FU and radiation on replication of interferon-expressing adenovirus

Abstract

Abstract Pancreatic Cancer is a disease for which there are very limited efficacious treatments, resulting in a 5-year survival rate for affected patients around only 6%. A recombinant oncolytic adenovirus (OAd-IFN) developed by our group to target pancreatic cancer utilizes enhanced oncolysis with an overexpression of the adenoviral death protein, enhanced infectivity with a genetically modified fiber, conditional replication targeted to pancreatic cancer using the Cox-2 promoter, and an expression of human interferonαto enhance the therapeutic effects of chemotherapy and radiation through the antitumor effects of the cytokine. Our previous work analyzing the therapeutic abilities of IFN expressing vectors in human pancreatic cancer xenografts in immonudeficient nude mice and in syngeneic hamster pancreatic cancer nodules in immunocompetent Syrian hamsters, showed a more evident antitumor effect of OAd-IFN in the latter models. This suggests the success of OAd-IFN as an immune system stimulator, making it a promising candidate for combination therapy approaches. The goal of this study is to investigate the possibility for use of OAd-IFN as a therapy for pancreatic cancer in conjunction with 5FU and radiation. Specifically, the adenoviral replicative ability was measured within pancreatic cancer Mia-Paca 2 cells under various conditions of 5FU and radiation exposure. Replication was analyzed by a correlation to the increase in amount of viral DNA extracted from treated cells at two time points post infection. In two preliminary trials, cells were infected with the virus two days prior to receiving 5FU and radiation, and another group of cells was treated with 5FU before viral infection. Based on the initial data collected, radiation seemed to have no effect on viral replication. 5FU treatment prior to viral infection resulted in an increase in replication at low dose, and a decrease in replication with high dose, however, this effect was only seen at the first time point 3 days after infection. Similarly, 5FU treatment post infection showed a minor dose dependent inhibition of viral replication at high doses, with little to no effect observed in the low dose. Combining viral infection with 5FU appears to have an impact on the replication of OAd-IFN in vitro; however, further trials need to be done to explore the effect of various timing among viral infection and therapy treatments as well as different therapy concentrations and viral titers to further analyze the potential combination therapies. Citation Format: Jordan Sell. Impact of 5FU and radiation on replication of interferon-expressing adenovirus. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1816. doi:10.1158/1538-7445.AM2015-1816