Effective gene-viral therapy of leukemia by a new fiber chimeric oncolytic adenovirus expressing TRAIL: in vitro and in vivo evaluation

J. Jin, H. Liu, C. Yang, G. Li, X. Liu, Q. Qian, W. Qian
2009 Molecular Cancer Therapeutics  
Conditionally replicating adenoviruses (CRAd) have been under extensive investigations as anticancer agents. Previously, we found that ZD55, an adenovirus serotype 5-based CRAd, infected and killed the leukemia cells expressing coxsackie adenovirus receptor (CAR). However, majority of leukemic cells lack CAR expression on their cell surface, resulting in resistance to CRAd infection. In this study, we showed that SG235, a novel fiber chimeric CRAd that has Ad35 tropism, permitted
more » ... cell entry, and this in turn produced selective cytopathic effects in a variety of human leukemic cells in vitro and in vivo. Moreover, SG235 expressing exogenous tumor necrosis factor-related apoptosis-inducing ligand (SG235-TRAIL) effectively induced apoptosis of leukemic cells via the activation of extrinsic and intrinsic apoptotic pathway and elicited a superior antileukemia activity compared with SG235. In addition, normal hematopoietic progenitors were resistant to the inhibitory activity of SG235 and SG235-TRAIL. Our data suggest that these novel oncolytic agents may serve as useful tools for the treatment of leukemia. [Mol Cancer Ther 2009;8(5):1387-97] Materials and Methods Primary Leukemia Samples, Cell Lines, and Reagents Bone marrow aspirates from the patients with acute myeloid leukemia (AML; n = 70), acute promyelocytic leukemia (n = 8), B-cell acute lymphocytic leukemia (n = 37), and T-cell acute lymphocytic leukemia (n = 7) were obtained
doi:10.1158/1535-7163.mct-08-0962 pmid:19417152 fatcat:3z3v5xfrqrdilovn53mlg6ecza