BACKGROUNDTo study the effect and safety of tissue specific gene therapy of suicide gene for lung adenocarcinoma.

METHODSRetroviral vector of G1CEACDNa contained a carcinoembryonic antigen (CEA) promoter regulated cytosine deaminase expression cassete (CEA/CD). By means of infection of virus, tissue specific expressing vectors and non-specific expressing vectors were transfected into A549 cell, which was CEA-producing lung adenocarcinoma cell line and then xenografted in nude mice, and the anti-tumor effect was evaluated. Then the retrovirus was injected directly into the tumor mass on nude mice, and the sensitivity of the xenograft to G1CEACDNa/5-fluorocytosine (5-FC) and the side effects were observed.

RESULTS(1) After transfected and untransfected A549 cells were implanted into nude mice, there was no difference in tumor formation among all the groups. (2) After 5-FC administration, the tumor transfected with tissue-specific gene displayed a higher sensitivity to the drug than those treated with non-specific in vitro gene-therapy. (3) The tumor-bearing nude mice were randomized in a blind manner based on comparable size to receive the supernatant of recombinant retrovirus G1CEACDNa followed by 5-FC, and significant growth suppression could be observed. (4) Comparing to the group with injection of 5-fluorouracil (5-FU) alone, tissue-specific suicide gene therapy showed lower suppression to bone marrow.

CONCLUSIONSThe results suggest that tissue-specific suicide gene therapy may play an important role in individual treatment of lung cancer.