Gene therapy with HSV-TK and IL-12 for nasopharyngeal carcinoma in nude mice
AIM: To investigate the therapeutic efficacy of adenovirus-mediated herpes simplex virus thymidine kinase (HSV-tk) gene transfer under the driving of KDR promoter (AdKDR-tk) combined with interleukin-12(IL-12) gene against of human nasopharyngeal carcinoma (NPC) in nude mice. METHODS: CNE-2 cell line was implanted subcutaneously into 36 nude mice, which were divided into 4 groups (n = 9 each group): IL-12 gene group, AdKDR-tk/GCV group, AdKDR-TK/GCV + IL-12 group and saline/GCV group. Selective intratumoral injection of recombinant adenovirus or saline was then given, which was repeated 24 h later. From the following day on, 10 d GCV was given at a dose of 100 mg/(kg · d) , ip. All the treated animals were killed and the tumor weight, the histopathological changes and the microvessel density of tumors were evaluated at the end of treatment. RESULTS: The tumor weight and microvessel density in IL-12 gene group, AdKDR-tk/GCV group, AdKDR-TK/GCV + IL-12 group and saline/GCV group were respectively (1.82 ± 0.78) g and (15.54 ± 3.46)/mm3; (1.61 ± 0.61) g and (10.69 ± 4.12)/mm3; (1.04 ± 0.52) g and (6.53 ± 1.61)/mm3; and (2.52 ± 1.18) g and (22.78 ± 5.12)/mm3. Growth and microvessel density of NPC were significantly inhibited in IL-12 gene group and AdKDR-tk/GCV group and AdKDR-TK/GCV + IL-12 group, compared with those in saline/GCV group (P ＜ 0.05). Significantly better antitumor effect was observed in IL-12 gene group, AdKDR-tk/GCV group and AdKDR-TK/GCV + IL-12 group, compared with that in saline/GCV group (P ＜ 0.05). CONCLUSION: Both HSV-tk and IL12 inhibit the growth of nasopharyngeal carcinoma in nude mice grafted subcutaneously and efficiently induce the host anti-tumor immune response. Combination of HSV-tk and IL 12 have some synergistic effect in anti-tumor treatment, which may offer a new treatment approach for human NPC.
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