Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Howard Hughes Medical Institute, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Cancer Res. 2022 Jul 5;82(13):2357-2360. doi: 10.1158/0008-5472.CAN-21-3799.
Circadian rhythms are the daily cycles that time almost all aspects of physiology, but treatments of the clock or by the clock are rarely tested in the clinic. We develop a framework for identifying interventions that may benefit from administration at the appropriate time of day (chronotherapy). Typically, pharmacokinetics is an important consideration for chronotherapy, with short half-life drugs deemed optimal for such treatments. However, recent data suggest long-lived antibodies can show time-of-day specific effects. Examples include both tumor-targeted antibodies as well as immunotherapies with antibodies that activate T cells. Clues to the immunotherapy mechanism come from animal vaccination studies, which demonstrate circadian responses of T cells to a single dose that leads to long-lasting T-cell activation. Conversely, some studies have challenged the efficacy of chronotherapy, underscoring the need to rigorously investigate its application for each drug and tumor type.
昼夜节律是时间几乎所有生理方面的日常循环，但对生物钟的治疗或由生物钟进行的治疗在临床上很少得到测试。我们开发了一个框架，用于确定可能受益于在适当的时间给药的干预措施（时间治疗学）。通常，药代动力学是时间治疗学的一个重要考虑因素，半衰期短的药物被认为是此类治疗的最佳选择。然而，最近的数据表明，寿命长的抗体可以显示出特定时间的效果。例子包括针对肿瘤的抗体以及通过激活 T 细胞的抗体进行的免疫疗法。免疫疗法机制的线索来自于动物疫苗接种研究，该研究表明 T 细胞对单次剂量的昼夜反应导致 T 细胞的长期激活。相反，一些研究对时间治疗学的疗效提出了质疑，这强调了需要严格研究每种药物和肿瘤类型的应用。
