Interleukin-2 therapy of cancer-clinical perspectives

Abstract

Interleukin (IL)-2 is a pleiotropic cytokine that displays opposing activities on immune system acting either in favor of or against cancer progression. Advanced/metastatic melanoma and renal cell carcinoma (RCC) are the two types of cancers that included most studies implemented for assessing the role of high-dose IL-2 therapy. The use of high-dose IL-2 therapy can, however, increase the rate of toxicities and interferes with the activity of endothelial cells (ECs) and effector T cells in tumor microenvironment (TME). This implies the need for adjusting strategies related to the cytokine therapy, such as suppressing signals that are interfering with the activity of this cytokine or the use of engineered IL-2 variants. The focus of this review is to discuss about pros and cons related to the IL-2 therapy and propose strategies to increase the efficacy of therapy. The outcomes of this literature will call for application of variants of IL-2 engineered to represent higher half-life and efficacy, and are more safe in the area of cancer immunotherapy.

Keywords: IL-2; Immune checkpoint inhibitor (ICI); Immunotherapy; Melanoma; Renal cell carcinoma (RCC); T cell; Toxicity; Tumor microenvironment (TME).