Kimura Yu, Mizuno Hiromi, Satake Kenichi, Tahara Hideaki, Tsukuda Mamoru
Department of Otolaryngology, Yokohama City University School of Medicine, Yokohama, Japan.
Arch Otolaryngol Head Neck Surg. 2003 Nov;129(11):1181-5. doi: 10.1001/archotol.129.11.1181.
The biological effects of cytokines are coming to be understood. The therapeutic effects of interleukin (IL) 2, IL-12, and interferon gamma (IFN-gamma) in cancer treatment have been reported, but there are problems when these cytokines are systemically used as therapeutic agents.
To examine the efficacy of IL-2 and IL-12 gene-transfected tumor cell vaccines for head and neck squamous cell carcinoma (SCC).
Homozygous mice with the autosomal recessive nude gene (BALB/c nu/nu mice) were inoculated subcutaneously in the right flank with cells from a human oral floor SCC cell line (KB cells). The mice were then injected with IL-2 and IL-12 gene-transfected KB cells (KB/IL-2 and KB/IL-12 cells, respectively) irradiated with 2000 rad (20 Gy).
No mice died soon after the injection of the gene immunotherapy. The treatment with either KB/human IL-2 (hIL-2) or KB/murine IL-12 (mIL-12) was not very effective. However, the treatment with both KB/hIL-2 and KB/mIL-12 cells significantly and safely inhibited the growth of established tumors (P =.04). There was no significant difference in antitumor effect between once-weekly and twice weekly injections of both KB/hIL-2 and KB/mIL-12 cells.
Double gene immunotherapy is safe and effective treatment for SCC in mice.
细胞因子的生物学效应正逐渐为人所了解。白细胞介素（IL）-2、IL-12和干扰素γ（IFN-γ）在癌症治疗中的疗效已有报道，但这些细胞因子作为治疗药物全身应用时存在问题。
研究IL-2和IL-12基因转染的肿瘤细胞疫苗对头颈部鳞状细胞癌（SCC）的疗效。
将携带常染色体隐性裸基因的纯合小鼠（BALB/c nu/nu小鼠）右腹侧皮下接种人舌底SCC细胞系（KB细胞）的细胞。然后给小鼠注射经2000拉德（20戈瑞）照射的IL-2和IL-12基因转染的KB细胞（分别为KB/IL-2和KB/IL-12细胞）。
基因免疫治疗注射后无小鼠很快死亡。单独用KB/人IL-2（hIL-2）或KB/鼠IL-12（mIL-12）治疗效果不佳。然而，联合使用KB/hIL-2和KB/mIL-12细胞能显著且安全地抑制已形成肿瘤的生长（P = 0.04）。每周注射一次和每周注射两次KB/hIL-2和KB/mIL-12细胞的抗肿瘤效果无显著差异。
双基因免疫治疗对小鼠SCC是一种安全有效的治疗方法。
