[Oncolytic property of HSV-1 recombinant viruses carrying the human IL-12]

Objective: Constructed the recombinant HSV-1 deleted ICP47 and inserted human IL-12, and investigate the virus' replication ability and oncolytic property in vitro and vivo. Methods: The recombinant HSV-1 deleting ICP47 (MH1005) and then inserting human IL-12 (MH1006) were obtained with bacterial artificial chromosome technology.The replication ability and the efficiency of inhibiting tumor were detected in several nerve tumor cell lines infected with HSV-wt, MH1005 and MH1006 respectively.The murine tumor model was established by subcutaneous inoculation Neuro-2a cells on both sides of mice back respectively.A dosage of 2×10(6) PFU of HSV-wt, MH1001(recombinant HSV-1 deleted IR), MH1005, MH1006 and Mock were injected 3 times intratumorally on one side of mice back in every 3 days, the tumor volume and survival rate of the mice were measured. Results: The replication abilities of MH1005, MH1006 and HSV-wt in 293FT cells were insignificant (P>0.05); the replication abilities of recombinant HSV-1 in G422 and Neuro-2a were higher than that in SK-N-SH; and the nerve tumor cells could be inhibited significantly by recombinant HSV-1.After 15 days of treatment, on the mouse backside with injection treatment, the tumor volumes of group HSV-wt (6 267±484), MH1001 (5 730±1 071), MH1005 (4 537±538)and MH1006 (4 150±476)mm(3) were smaller than that of group Mock (6 957±722) mm(3) significantly (all P<0.01); on the mouse backside without injection treatment, the tumor volumes of group MH1005 (5 952±607) and MH1006 (5 473±661) mm(3) were smaller than those of HSV-wt (6 785±1 063), MH1001 (6 774±808) and Mock (6 957±190) mm(3) significantly (all P<0.05); after 35 days of treatment, the mice survival rates of group MH1005 (100%) and MH1006 (100%) were higher than those of MH1001 (67%), HSV-wt (50%) and Mock (33%) significantly (all P<0.05). Conclusion: MH1005 and MH1006 can infect nerve tumor cells and replicate at high level, the viruses not only kill tumor cells directly but also induce immunological rejection to tumor, and prolong the survival of mice bearing tumor.