Fehniger Todd A, Cooper Megan A, Caligiuri Michael A
Department of Internal Medicine, Division of Hematology/Oncology, The Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Cytokine Growth Factor Rev. 2002 Apr;13(2):169-83. doi: 10.1016/s1359-6101(01)00021-1.
Interleukin (IL)-2 and IL-15 are two cytokine growth factors that regulate lymphocyte function and homeostasis. Early clinical interest in the use of IL-2 in the immunotherapy of renal cell carcinoma and malignant melanoma demonstrated the first efficacy for cytokine monotherapy in the treatment of neoplastic disease. Advances in our understanding of the cellular and molecular biology of IL-2 and its receptor complex have provided rationale to better utilize IL-2 to expand and activate immune effectors in patients with cancer. Exciting new developments in monoclonal antibodies recognizing tumor targets and tumor vaccines have provided new avenues to combine with IL-2 therapy in cancer patients. IL-15, initially thought to mediate similar biological effects as IL-2, has been shown to have unique properties in basic and pre-clinical studies that may be of benefit in the immunotherapy of cancer. This review first summarizes the differences between IL-2 and IL-15 and highlights that better understanding of normal physiology creates new ideas for the immunotherapy of cancer. The application of high, intermediate, and low/ultra low dose IL-2 therapy in clinical trials of cancer patients is discussed, along with new avenues for its use in neoplastic diseases. The growing basic and pre-clinical evidence demonstrating that IL-15 may be useful in immunotherapy approaches to cancer is also presented.
白细胞介素（IL）-2和IL-15是两种调节淋巴细胞功能和内环境稳定的细胞因子生长因子。早期临床对IL-2用于肾细胞癌和恶性黑色素瘤免疫治疗的兴趣表明，细胞因子单一疗法在肿瘤疾病治疗中首次显示出疗效。我们对IL-2及其受体复合物的细胞和分子生物学认识的进展，为更好地利用IL-2来扩增和激活癌症患者的免疫效应细胞提供了理论依据。识别肿瘤靶点的单克隆抗体和肿瘤疫苗方面令人兴奋的新进展，为癌症患者中与IL-2疗法联合应用提供了新途径。IL-15最初被认为介导与IL-2相似的生物学效应，但在基础和临床前研究中已显示出具有独特特性，这可能对癌症免疫治疗有益。本综述首先总结了IL-2和IL-15之间的差异，并强调对正常生理学的更好理解为癌症免疫治疗带来了新思路。讨论了高、中、低/超低剂量IL-2疗法在癌症患者临床试验中的应用，以及其在肿瘤疾病中的新应用途径。还介绍了越来越多的基础和临床前证据，表明IL-15可能在癌症免疫治疗方法中有用。
