[Anti-tumor effect of lentivirus-mediated MUCI antibody-targeted gene therapy with VP22-TK system on MUC1(+) human ovarian cancer transplanted intraperitoneally in nude mice].
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.


CONCLUSIONS
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.
Kong
Beihua
B
Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, China.
Wang
Wenxia
W
Liu
Chungsheng
C
Ma
Daoxin
D
Qu
Xun
X
Jiang
Jie
J
Yang
Xingsheng
X
Zhang
Youzhong
Y
Jiang
Sen
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007128:Immunoglobulin Fragments / Q000008:administration & dosage / Q000276:immunology; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018396:Mucin-1 / Q000276:immunology*; D009368:Neoplasm Transplantation / Q000379:methods; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D011897:Random Allocation; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics; D016019:Survival Analysis; D013937:Thymidine Kinase / Q000235:genetics*; D014407:Tumor Cells, Cultured; D015678:Viral Structural Proteins / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007128:Immunoglobulin Fragments; D018396:Mucin-1; D011993:Recombinant Fusion Proteins; D015678:Viral Structural Proteins; C073413:herpes simplex virus type 1 protein VP22; D013937:Thymidine Kinase