Abstract
T-cell-stimulating cytokines have shown promise as monotherapies or in combination with other therapeutic modalities for immunotherapy of cancer. However, their efficacy is limited due to their short half-life, pleiotropic roles, and induction of severe toxicity even at therapeutic doses. To overcome these major therapeutic barriers, cytokine-based products are being further developed to improve their therapeutic index. These approaches include manipulating their activity to preferentially bind to effector immune cells rather than immune-suppressive cells, prolonging their half-life in vivo and modifying them to target tumors. This review focuses on IL-2, IL-15, and IL-10, which have potent effects on immune cells that mediate effective antitumor responses. We will summarize the recent progress of these cytokines in both preclinical studies and selective clinical applications and will discuss our perspectives on the development of new strategies to potentiate cytokine-based immunotherapy.