[Effects of KH901, a tumor-specific oncolytic recombinant adenovirus, on antitumor and expressing GM-CSF in xenograft tumor models].
OBJECTIVE
Conditionally replicating oncolytic adenovirus KH901 was engineered with a genetically modified telomerase reverse transcriptase promoter and a cDNA of human granulocyte macrophage colony stimulating factor (GM-CSF). The objective of this study was to evaluate the anti-tumor efficacy and the selective GM-CSF expression of KH901 in xenograft tumor models.


METHODS
After intratumoral administration of KH901, the rates of Relative Tumor Growth (T/C%) and inhibition in Hep3B and LNcap xenograft models were measured for observing the KH901 antitumor efficacy. At various time points, the GM-CSF expression levels in tumor tissues and the blood of A549 xenograft model were determined by ELISA method.


RESULTS
In both Hep3B and LNcap xenograft models, KH901 showed the significantly higher restraint tumor rates at high dose (3 X 10(10) VP, P<0. 05) compared to 5-FU or Cisplatin. Even at the low dose (3 X 10(8) VP), the KH901 antitumor effect was similar to 5-FU (P>0. 05). In A549 xenograft model, the level of GM-CSF was continuously elevated and the peak values were found on day 7 in the blood and on day 11 in the tumor tissues. Then GM-CSF expression gradually reduced in both blood and tumor tissues.


CONCLUSIONS
KH901 can significantly inhibit the tumor growth in xenograft tumor model, and also express a high level of human GM-CSF in tumor tissue and release to circulating system to form a CM-CSF peak value in the blood.
Shen
Fu-bing
FB
National Chengdu Center of Safety Evaluation of Traditional Chinese Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Yang
Chun
C
Lei
Ning
N
Ju
Qing
Q
Guo
Yong
Y
Yi
Bo
B
Luo
Zu-xiu
ZX
Li
Hong-xia
HX
Wang
Li
L
D000256:Adenoviridae / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D004274:DNA, Recombinant / Q000235:genetics*; D004195:Disease Models, Animal; D015870:Gene Expression; D005818:Genetic Engineering; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology*; D050504:Oncolytic Viruses / Q000235:genetics* / Q000502:physiology*
D004274:DNA, Recombinant; D016178:Granulocyte-Macrophage Colony-Stimulating Factor