175 Coxsackievirus A11 Possesses Extensive Oncolytic Activity Against Human Non Small Cell Lung Cancer Cells Molecular Therapy Volume 22, Supplement 1, May 2014 Copyright © The American Society of Gen[.]
CANCER-ONCOLYTIC VIRUSES I anti-tumor therapeutic both to the tumor cells themselves and to their supporting stroma We therefore transduced MSCs with ICOVIR15 and a replication incompetent Adenovirus carrying the GFP gene (Ad.GFP) days later, supernatant was transferred from the MSCs to lung cancer cell lines A549 and H1299 The tumor cells (99%) initially became GFP positive, due to the transgene derived from the Rid, and then died, due to the cytopathic effects of the ICOVIR15 (70% Annexin V positivity) Hence MSCs can replicate and release both viruses The MSCs transduced with ICOVIR15 produce 32 fold more RIAd vectors than MSCs expressing E1A alone This experiment was repeated using an ICOVIR-15 in combination with a RIAd vector encoding iC9 and truncated CD19 (Ad.iC9) as a marker The transduction efficiency of A549 tumor cells was measured by their CD19-positivity and was 16 fold higher than tumors exposed to supernatants from MSCs expressing E1A alone and without the ICOVIR15 CRAD To test the anti-tumor effect of this therapy, SCIDBeige mice were injected IV with FFLuc labeled A549 cells (n=10/ group) Mice were then treated with control MSCs, ICOVIR15-MSCs, iC9-MSCs or ICOVIR15-iC9-MSCs IV weekly x The mice that received iC9-MSCs were treated with IP CID every other day for a total of doses/week The ICOVIR15-iC9-MSCs group consistently showed better tumor control (3.03E+9 signal change) compared to mice receiving control MSCs (3.70E+10), iC9-MSCs (6.8E+10,) (p=50 weeks Furthermore, the oncolytic activity was evaluated by a single intraperitoneal injection of each virus (106 pfu) in SCID mice bearing peritoneally disseminated BxPC3 xenografts VGF-/O1-VV significantly prolonged survival compared with VGF-VV (P=0.031), O1-VV (P=0.0018), VGF+/ O1+VV (P=0.0023) and mock therapy (P=0.0047) Importantly, the S67 ... we showed that CVA11 displayed remarkable oncolytic activity against human NSCLC both in vitro and in vivo with tolerability, presumably via the receptor ICAM-1 and resultant cell death machinery... were much more dramatically reduced by serum starvation in the normal cells compared with the tumor cells In serum-starved NHLF cells, VGF-/O1-VV infection did not upregulate the pERK1/2 levels compared... virus genes would inhibit pathogenic viral replication in normal cells, while retaining its therapeutic replication in tumor cells that have the constitutive ERK1/2 activation Our study is the