Cytokine Therapeutics in Cancer Immunotherapy: Design and Development

Abstract

In this article, recent advances in the application of cytokine therapeutics in cancer, as single agents or in combination with other immunotherapies, are reviewed. Additionally, critical characteristics that govern cytokine exposure-response properties are discussed. Immunotherapy has revolutionized the traditional approach to treating cancer. Targeted therapies, via modulation of the host immune responses, have elevated the expectations for a beneficial impact on patients’ lives. Novel drugs that modulate various steps in the cancer-immunity cycle are now available with an impact on both the magnitude and duration of effect relative to traditional chemotherapeutic approaches. Due to cancer heterogeneity, induction of effective anti-tumor immunity requires the orchestration of several critical events, and hence, combination approaches are being explored. Combination immunotherapy is anticipated to enhance the durability and efficacy profiles of otherwise single agents that can benefit from the “synergistic” effects from the engagement of two or more pathways, simultaneously. As cytokines regulate many aspects of innate and adaptive immunity, application of cytokines in cancer immunotherapy has attracted considerable attention. Application of cytokines in the treatment of cancer is limited by their pleiotropic effects, toxicity at required clinical doses, and unfavorable pharmacokinetic properties. Recent advances in protein engineering have now made it possible to improve the undesirable properties of these biologics. Additionally, the recent breakthroughs in the treatment of cancer, using immunotherapies, have renewed interest in evaluating cytokines and their variants in combination regiments to improve immunity against malignant cells.