E1B 55‐kDa deleted, Ad5/F35 fiber chimeric adenovirus, a potential oncolytic agent for B‐lymphocytic malignancies

Abstract Background Conditionally replicative adenovirus (CRAd) provides a promising strategy for solid tumor therapy. However, relatively few studies have been addressed on hematopoietic malignancies. We previously found that ZD55, a serotype 5 (Ad5)‐based, E1B 55‐kDa deleted CRAd, inhibited leukemic cell growth and induced apoptosis. In the present study, we employed SG235, a new CRAd with both an E1B 55‐kDa deletion and an Ad5/F35 chimeric fiber, for the treatment of B‐cell tumors. Methods CRAd SG235 was engineered not to express adenovirus E1B 55‐kDa gene, and the wild‐type Ad5 fiber was replaced by a chimeric Ad5/35 fiber containing an Ad5 tail, an Ad35 shaft and an Ad35 knob. Using in vitro and in vivo experiments, the infectivity and selective cytotoxicity of SG235 on B‐cell tumor lines were evaluated. Apoptosis‐related signaling elements were investigated. Results SG235 significantly suppressed malignant B‐cell growth in vitro and in vivo . In addition to selective cytolysis, SG235‐induced apoptosis in the tumor cells. Upon SG235 infection, levels of cleaved forms of caspase‐3 and poly(adenosine diphosphate‐ribose) polymerase increased, suggesting that SG235 induces apoptosis in malignant B‐cells by activating a caspase cascade. Furthermore, SG235 infection resulted in an up‐regulated level of Bax, as well as down‐regulated levels of xIAP, cIAP and survivin, suggesting that infection of SG235 induces apoptosis in B‐cell tumor lines by affecting both apoptosis‐promoting and ‐inhibiting intracellular signaling elements. Conclusions CRAd SG235 may serve as a potential anticancer agent, or a therapeutic vehicle for harboring anticancer genes, in B‐cell tumor treatment. Copyright © 2009 John Wiley & Sons, Ltd.