Coventry Brendon J, Ashdown Martin L
Discipline of Surgery, University of Adelaide, Royal Adelaide Hospital and Faculty of Medicine, University of Melbourne, Australia.
Cancer Manag Res. 2012;4:215-21. doi: 10.2147/CMAR.S33979. Epub 2012 Aug 2.
This year marks the twentieth anniversary of the approval by the US Food and Drug Administration of interleukin-2 (IL2) for use in cancer therapy, initially for renal cell carcinoma and later for melanoma. IL2 therapy for cancer has stood the test of time, with continued widespread use in Europe, parts of Asia, and the US. Clinical complete responses are variably reported at 5%-20% for advanced malignant melanoma and renal cell carcinoma, with strong durable responses and sustained long-term 5-10-year survival being typical if complete responses are generated.
The literature was reviewed for the actions and clinical effects of IL2 on subsets of T cells. The influence of IL2 on clinical efficacy was also sought.
The review revealed that IL2 is capable of stimulating different populations of T cells in humans to induce either T effector or T regulatory responses. This apparent "functional paradox" has confounded a clear understanding of the mechanisms behind the clinical effects that are observed during and following administration of IL2 therapy. An average complete response rate of around 7% in small and large clinical trials using IL2 for advanced renal cell carcinoma and malignant melanoma has been shown from a recent review of the literature.
This review considers the published literature concerning the actions and emerging clinical effects of IL2 therapy, spanning its 20-year period in clinical use. It further details some of the recently described "bimodal" effects of IL2 to explain the apparent functional paradox, and how IL2 might be harnessed to emerge rapidly as a much more effective and predictable clinical agent in the near future.
今年是美国食品药品监督管理局批准白细胞介素-2（IL2）用于癌症治疗二十周年，最初用于肾细胞癌，后来用于黑色素瘤。IL2癌症治疗经受住了时间的考验，在欧洲、亚洲部分地区和美国仍被广泛使用。晚期恶性黑色素瘤和肾细胞癌的临床完全缓解率报告不一，为5%-20%，如果产生完全缓解，典型情况是有强烈的持久反应和持续的5至10年长期生存。
回顾了关于IL2对T细胞亚群作用和临床效果的文献。还探讨了IL2对临床疗效的影响。
综述显示，IL2能够刺激人类不同群体的T细胞，诱导T效应或T调节反应。这种明显的“功能悖论”使人们难以清楚理解在IL2治疗期间及之后观察到的临床效果背后的机制。最近对文献的综述表明，在使用IL2治疗晚期肾细胞癌和恶性黑色素瘤的小型和大型临床试验中，平均完全缓解率约为7%。
本综述考虑了已发表的关于IL2治疗作用和新出现临床效果的文献，涵盖其20年临床使用期。它进一步详细阐述了IL2最近描述的一些“双峰”效应，以解释明显的功能悖论，以及在不久的将来如何利用IL2迅速成为一种更有效、更可预测的临床药物。
