白细胞介素-12临床应用研究进展  

Study of interleukin-12 clinical uses

作　　者：宋舸[1] 袁玫[1] 卢世璧[1] 

机构地区：[1]中国人民解放军总医院骨科研究所,北京100853

出　　处：《中华肿瘤防治杂志》2007年第1期75-79,共5页Chinese Journal of Cancer Prevention and Treatment

摘　　要：白细胞介素-12(IL-12)最初称作自然杀伤细胞刺激因子(NKSF)或细胞毒性淋巴细胞成熟因子(CLMF),是一种异二聚体细胞因子。直接使用重组蛋白IL-12或转基因载体都有显著的抗肿瘤作用,它通过诱发NK,NKT和T细胞增殖活化而介导主动和被动免疫保护反应。除此之外,通过趋化因子IP-10诱生IFN-γ阻止肿瘤血管发生。在动物肿瘤模型中,IL-12对移植瘤、化学诱变瘤及自发肿瘤均有明显治疗作用。IL-12可以刺激抗原特异性免疫反应而促进Th1和CTL的消瘤作用。大量的临床治疗肿瘤试验表明,IL-12在抗肿瘤方面效果明显。治疗中出现的不良反应应引起重视,需要制定合理的治疗方案以降低毒副反应确保临床效果。Interleukin-12 （IL-12） previously called cytotoxic lymphocyte maturation factor （CLMF） or NK cell stimulatory factor （NKSF） is a recently characterized heterodimeric cytokine composed of two subunits. IL-12 has demonstrated remarkable antitumor activity when used directly as a recombinant protein or when different viral or non-viral vectors transfer its genes. At enhancing tumor immunity, IL-12 acts as a bridge between innate and adaptive immune responses due to its ability to induce proliferation and activation of NK, NKT, and T cells. In addition, IL-12 inhibits tumor angiogenesis mainly through IFN-T gamma-dependent production of the chemokine IP-10. In experimental tumor models, recombinant IL-12 treatment has a dramatic anti-tumor effect on transplantable tumors, on chemically induced tumors, and in tumors arising spontaneously in genetically modified mice. The stimulating activity of IL-12 on antigen-specific immunity relies mostly on its ability to determine or augment Th1 and cytotoxic T lymphocyte responses. Because of this ability, IL-12 has a potent adjuvant activity in cancer and other vaccines. The promising data obtained in the clinical models of antitumor immunotherapy have raised much hope that IL-12 could be a powerful therapeutic agent against cancer. However, excessive clinical toxicity and modest clinical response observed in the clinical trials point to the necessity to plan protocols that minimize toxicity without affecting the antitumor effect of IL-12.

关 键 词：白细胞介素-12 伽马-干扰素 肿瘤/免疫 临床治疗/免疫 综述文献 

分 类 号：R730.2[医药卫生—肿瘤]