Floros Theofanis, Tarhini Ahmad A
University of Pittsburgh Cancer Institute, Pittsburgh, PA; Athens Naval and Veterans Hospital, Pittsburgh, PA.
University of Pittsburgh Cancer Institute, Pittsburgh, PA; University of Pittsburgh School of Medicine, Pittsburgh, PA.
Semin Oncol. 2015 Aug;42(4):539-48. doi: 10.1053/j.seminoncol.2015.05.015. Epub 2015 Jun 3.
Efforts over nearly four decades have focused on ways to use cytokines to manipulate the host immune response towards cancer cell recognition and eradication. Significant advances were achieved with interleukin-2 (IL-2) and interferon-α (IFN-α), primarily in the treatment of patients with melanoma and renal cell carcinoma. However, the utility of other cytokines showing promise in the preclinical setting has not been established largely because of toxicity, the complex functionality of each cytokine and the difficulty mimicking in preclinical models the human environment. Here, we review the basic biology and the clinical experiences with IFN-α, IL-2, IL-15, IL-21, and IL-12. We will also review ongoing clinical trials and discuss future directions including potential use of cytokines in combination with other effective immunotherapy approaches that have come of age in recent years.
近四十年来的研究致力于探寻利用细胞因子来调控宿主免疫反应以识别和根除癌细胞的方法。白细胞介素-2（IL-2）和干扰素-α（IFN-α）取得了重大进展，主要用于治疗黑色素瘤和肾细胞癌患者。然而，其他在临床前研究中显示出前景的细胞因子尚未得到广泛应用，这主要是由于毒性、每种细胞因子复杂的功能以及在临床前模型中难以模拟人类环境。在此，我们综述了IFN-α、IL-2、IL-15、IL-21和IL-12的基础生物学及临床经验。我们还将综述正在进行的临床试验，并讨论未来的方向，包括细胞因子与近年来已成熟的其他有效免疫治疗方法联合使用的潜在可能性。
