{"title":"Engineering cytokines for tumor-targeting and selective T cell activation.","authors":"Kun Peng, Yang-Xin Fu, Yong Liang","doi":"10.1016/j.molmed.2025.01.010","DOIUrl":null,"url":null,"abstract":"<p><p>Cytokines are promising therapeutic agents for cancer due to their immune-stimulating properties. However, their clinical application is limited by a narrow therapeutic window and dose-limiting on-target, off-tumor toxicity. Advances in protein engineering enable the selective delivery of cytokines to the tumor microenvironment (TME) and antigen-specific T cells, enhancing antitumor efficacy while reducing systemic side effects. This review focuses on selected cytokines and outlines their developmental trajectory for treating solid tumors. We highlight strategies for constructing cis-signaling immunocytokines and procytokines for precise delivery to tumor sites and discuss the biological mechanisms through which these cytokines reactivate antitumor immunity. We also discuss the challenges and future directions for creating more effective cytokine-based therapeutics.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8000,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in molecular medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.molmed.2025.01.010","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Cytokines are promising therapeutic agents for cancer due to their immune-stimulating properties. However, their clinical application is limited by a narrow therapeutic window and dose-limiting on-target, off-tumor toxicity. Advances in protein engineering enable the selective delivery of cytokines to the tumor microenvironment (TME) and antigen-specific T cells, enhancing antitumor efficacy while reducing systemic side effects. This review focuses on selected cytokines and outlines their developmental trajectory for treating solid tumors. We highlight strategies for constructing cis-signaling immunocytokines and procytokines for precise delivery to tumor sites and discuss the biological mechanisms through which these cytokines reactivate antitumor immunity. We also discuss the challenges and future directions for creating more effective cytokine-based therapeutics.
期刊介绍：
Trends in Molecular Medicine (TMM) aims to offer concise and contextualized perspectives on the latest research advancing biomedical science toward better diagnosis, treatment, and prevention of human diseases. It focuses on research at the intersection of basic biology and clinical research, covering new concepts in human biology and pathology with clear implications for diagnostics and therapy. TMM reviews bridge the gap between bench and bedside, discussing research from preclinical studies to patient-enrolled trials. The major themes include disease mechanisms, tools and technologies, diagnostics, and therapeutics, with a preference for articles relevant to multiple themes. TMM serves as a platform for discussion, pushing traditional boundaries and fostering collaboration between scientists and clinicians. The journal seeks to publish provocative and authoritative articles that are also accessible to a broad audience, inspiring new directions in molecular medicine to enhance human health.
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