[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.

CONCLUSION: 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.