Engineering cytokines for cancer immunotherapy: a systematic review

免疫疗法 医学 细胞因子 癌症免疫疗法 肿瘤微环境 癌症 临床试验 免疫系统 免疫学 癌症研究 内科学
作者
Yong Fu,Renhong Tang,Xiaofeng Zhao
出处
期刊:Frontiers in Immunology [Frontiers Media]
卷期号:14 被引量:3
标识
DOI:10.3389/fimmu.2023.1218082
摘要

Cytokines are pivotal mediators of cell communication in the tumor microenvironment. Multiple cytokines are involved in the host antitumor response, but the production and function of these cytokines are usually dysregulated during malignant tumor progression. Considering their clinical potential and the early successful use of cytokines in cancer immunotherapy, such as interferon alpha-2b (IFNα-2b; IntronA®) and IL-2 (Proleukin®), cytokine-based therapeutics have been extensively evaluated in many follow-up clinical trials. Following these initial breakthroughs, however, clinical translation of these natural messenger molecules has been greatly limited owing to their high-degree pleiotropic features and complex biological properties in many cell types. These characteristics, coupled with poor pharmacokinetics (a short half-life), have hampered the delivery of cytokines via systemic administration, particularly because of severe dose-limiting toxicities. New engineering approaches have been developed to widen the therapeutic window, prolong pharmacokinetic effects, enhance tumor targeting and reduce adverse effects, thereby improving therapeutic efficacy. In this review, we focus on the recent progress and competitive landscape in cytokine engineering strategies and preclinical/clinical therapeutics for cancer. In addition, aiming to promote engineered cytokine-based cancer immunotherapy, we present a profound discussion about the feasibility of recently developed methods in clinical medicine translation.
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