title: 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.
authors.affiliation: Institute of Hematology, First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Wang
authors.forename: Gongchu
authors.initials: G
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Chunmei
authors.initials: C
authors.lastname: Yang
authors.forename: Xiudi
authors.initials: X
authors.lastname: Yang
authors.forename: Jie
authors.initials: J
authors.lastname: Jin
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Liu
authors.forename: Qijun
authors.initials: Q
authors.lastname: Qian
authors.forename: Wenbin
authors.initials: W
authors.lastname: Qian