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白细胞介素2与白细胞介素12基因转染肿瘤疫苗联合治疗对头颈部癌的疗效

Effects of combined therapy with interleukin 2 and interleukin 12 gene-transfected tumor vaccine for head and neck carcinoma.

作者信息

Kimura Yu, Mizuno Hiromi, Satake Kenichi, Tahara Hideaki, Tsukuda Mamoru

机构信息

Department of Otolaryngology, Yokohama City University School of Medicine, Yokohama, Japan.

出版信息

Arch Otolaryngol Head Neck Surg. 2003 Nov;129(11):1181-5. doi: 10.1001/archotol.129.11.1181.

Abstract

BACKGROUND

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.

OBJECTIVE

To examine the efficacy of IL-2 and IL-12 gene-transfected tumor cell vaccines for head and neck squamous cell carcinoma (SCC).

METHODS

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).

RESULTS

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.

CONCLUSION

Double gene immunotherapy is safe and effective treatment for SCC in mice.

摘要

背景

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。

目的

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。

方法

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)。

结果

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。

结论

双基因免疫治疗对小鼠SCC是一种安全有效的治疗方法。

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