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.
©2022 American Association for Cancer Research.