Potent antitumor effect of interleukin-24 gene in the survivin promoter and retinoblastoma double-regulated oncolytic adenovirus.
Interleukin (IL)-24 is an excellent therapeutic gene for cancer therapy. In this work, IL-24 was inserted into Ad.sp-E1A(Delta24), an oncolytic adenovirus with a 24-bp deletion in the E1A gene, which was driven by the survivin promoter to form Ad.sp-E1A(Delta24)-IL-24. Ad.sp-E1A(Delta24)-IL-24 has an excellent antitumor effect in vitro for human nasopharyngeal, liver, lung, and cervical carcinoma cell lines but does no or little damage to normal cell lines L-02 and WI38. Furthermore, it achieved nearly complete inhibition (although not elimination) of NCI-H460 lung carcinoma growth in nude mice. The antitumor efficacy of Ad.sp-E1A(Delta24)-IL-24 on NCI-H460 cells was clearly mediated by apoptosis, because it induced caspase-3 and poly(ADP-ribose) polymerase cleavage. This is the first report of Ad.sp-E1A(Delta24)-IL-24 with such an excellent, broad, and specific antitumor effect in vitro and nearly complete inhibition of lung tumor growth in vivo.
Zhang
Kang Jian
KJ
School of Life Sciences, Xinyuan Institute of Medicine and Biotechnology, Zhejiang Sci-Tech University, Hangzhou 310018, China.
Wang
Yi Gang
YG
Cao
Xin
X
Zhong
Su Yang
SY
Wei
Rui Cheng
RC
Wu
Yu Mei
YM
Yue
Xue Tian
XT
Li
Gong Chu
GC
Liu
Xin Yuan
XY