Brunda M J, Gately M K
Department of Oncology, Hoffmann-La Roche, Inc. Nutley, New Jersey, USA.
Important Adv Oncol. 1995:3-18.
IL-12 is a heterodimeric cytokine that promotes cell-mediated immunity through its regulatory effects on T and NK cells. IL-12 produced endogenously in response to various microbial agents likely plays a role in the host response to infection by intracellular pathogens, and administration of rIL-12 to mice has bee shown to have dramatic therapeutic effects in a number of tumor models and models of infectious diseases. The relatively long serum half-life of IL-12 compared to other lower molecular weight cytokines such as IL-2 should permit more flexibility in dose scheduling. At doses which are efficacious in murine tumor models, IL-12 has been well tolerated. Phase I clinical trials with IL-12 in the treatment of human malignancies have recently been initiated. The results of such studies are required to determine whether the therapeutic potential IL-12 has displayed in murine disease models can be translated into clinical utility in man.
白细胞介素-12是一种异二聚体细胞因子,通过对T细胞和自然杀伤(NK)细胞的调节作用来促进细胞介导的免疫。内源性产生的白细胞介素-12可响应各种微生物因子,可能在宿主对细胞内病原体感染的反应中发挥作用,并且已证明给小鼠施用重组白细胞介素-12在许多肿瘤模型和传染病模型中具有显著的治疗效果。与其他低分子量细胞因子(如白细胞介素-2)相比,白细胞介素-12相对较长的血清半衰期应使剂量安排更具灵活性。在对小鼠肿瘤模型有效的剂量下,白细胞介素-12耐受性良好。最近已启动白细胞介素-12治疗人类恶性肿瘤的I期临床试验。需要此类研究的结果来确定白细胞介素-12在小鼠疾病模型中显示出的治疗潜力是否可以转化为人类的临床应用。