Objective: To investigate the anti-tumor effect of anti-MUCI single-chain variable fragment (ScFv)-targeted and lentivirus-mediated herpes simplex virus structural protein VP22 and thymidinre kinase (TK) therapy on MUC1(+) human ovarian epithelial carcinoma tumor in mice transplanted intraperitoneally.
Methods: Lentiviruses scFv-VP22-TK and VP22-TK were constorted Ten female BABL/c mice were injected intraperitoneally with MUC1+ human ovarian epithelial carcinoma cells line 3AO and then pathological examination was done to those mice that died of tumor. A human ovarian epithelial carcinoma model was established in another 30 female mice and they were randomly divided into 6 groups of 5 mice: NS (normal saline) + NS group (injected intraperitoneally with NS once per day for 3 days and then with NS 24 h after once a day for 5 days), VP22-TK + NS group (injected with herpes simplex virus structural protein VP22 and TK once a day for three days and then with NS 24 h after once a day for 5 days), scFv-VP22-TK + NS group (injected with scFv-VP22-TK and then NS in the same way), NS + ganciclovir (GCV) group (injected with NS and then with GCV), VP22-TK + GCV group (injected with VP22-TK and then GCV), and scFv-VP22-TK + GCV group (injected with scFv-VP22-TK and then GCV). The survival time was observed. Ten female nude mice without injection of tumor cells were injected with scFv-VP22-TK or VP22-TK, each for 5 mice; 3 weeks later their abdominal organs were examined to observe the effects of lentivirus on organs.
Results: All of the first ten mice injected with human ovarian epithelial carcinoma cells died of tumor. The mean survival times of the six experimental groups were 18.4 d +/- 2.9 d, 18.8 d +/- 1.5 d, 17.6 d +/- 1.1 d, 18.5 d +/- 1.6 d, 24 d +/- 5 d, and 46 d +/- 22 d respectively with significant differences between the VP22-TK + GCV group and NS + GCV group (chi(2) = 6.71, P = 0.009), between the scFv-VP22-TK + GCV group and NS + GCV group (chi(2) = 9.7, P = 0.002), and between the scFv-VP22-TK + GCV group and the VP22-TK + GCV group (chi(2) = 7.43, P = 0.006). Necrosis and apoptosis could be seen in the tumors in the VP22-TK + GCV group and scFV-VP22-TK + GCV group. No toxicity was observed in the mice injected with only scFv-VP22-TK or VP22-TK.
Conclusion: The anti-MUCI ScFv-targeted and lentivirus-mediated herpes simplex virus VP22 and thymidinre kinase (TK) gene therapy has a significant anti-tumor effect on MUC1+ human ovarian epithelial carcinoma.