Boiron M
Nouv Rev Fr Hematol (1978). 1987;29(1):49-55.
The anti-tumour effects of interferons (IFNs) in animals and man are well known. However, despite the fact that the three types of human IFNs, leukocyte alpha-IFN, fibroblast beta-IFN and immune gamma-IFN, are available in large amounts through recombinant DNA technology, the practical applicability of IFN therapy in cancer is far from clear. An initial approach to this problem is to determine the mechanism of action of IFNs and, if they do not act, to find out why. There are various ways in which IFN may control tumours, i.e. anti-viral action, inhibition of cell growth, stimulation of cell differentiation, changes in cells modulating the susceptibility to immune rejection, or effects on the host immune systems (natural killer system and cytotoxic proteins). The implications of these data for the use of IFNs in cancer therapy then need to be evaluated. Both alpha- and beta-IFNs may have beneficial effects on growth inhibition and differentiation, but gamma-IFN is probably stronger in boosting the immune recognition and rejection of tumour cells. A combination of these two types of IFNs may give the best results in vivo since they often act synergistically in vitro. The sensitivity of individual tumour cells to the various types of IFN needs to be evaluated to select the best treatment by measuring oncogene mRNA inhibition, G0/G1 arrest and increase in various HLA antigens. Finally, the aim of any treatment (anti-viral action, tumour regression, prevention of metastasis, decreased tumour growth and increased cell differentiation) should be an important consideration in choosing IFN therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
干扰素(IFN)在动物和人类中的抗肿瘤作用已广为人知。然而,尽管通过重组DNA技术可大量获得三种类型的人干扰素,即白细胞α-干扰素、成纤维细胞β-干扰素和免疫γ-干扰素,但IFN疗法在癌症治疗中的实际适用性仍远不明确。解决这一问题的初步方法是确定IFN的作用机制,如果其不起作用,则找出原因。IFN可能通过多种方式控制肿瘤,即抗病毒作用、抑制细胞生长、刺激细胞分化、改变细胞调节免疫排斥易感性,或对宿主免疫系统(自然杀伤系统和细胞毒性蛋白)产生影响。然后需要评估这些数据对IFN用于癌症治疗的意义。α-干扰素和β-干扰素可能对生长抑制和分化有有益作用,但γ-干扰素在增强免疫识别和肿瘤细胞排斥方面可能更强。这两种类型的干扰素联合使用可能在体内产生最佳效果,因为它们在体外通常具有协同作用。需要通过测量癌基因mRNA抑制、G0/G1期阻滞以及各种HLA抗原的增加来评估单个肿瘤细胞对不同类型IFN的敏感性,以选择最佳治疗方案。最后,在选择IFN治疗时,任何治疗的目标(抗病毒作用、肿瘤消退、预防转移、降低肿瘤生长和增加细胞分化)都应是一个重要的考虑因素。(摘要截短于250字)