重组细胞因子产品因其调节和增强针对肿瘤的免疫反应的能力而成为癌症治疗的一个有前途的途径。然而，它们的临床应用受到低剂量时的全身毒性的严重阻碍，从而阻碍了升级至治疗活性方案。克服这些限制的一种有前景的方法是使用抗体-细胞因子融合蛋白（也称为免疫细胞因子）。这些生物药物利用抗体的靶向特异性将细胞因子直接递送至肿瘤微环境，从而减少全身暴露并提高治疗指数。这篇综述全面探讨了抗体-细胞因子融合蛋白在癌症治疗中的发展和潜力。它探讨了影响这些融合蛋白性能的分子特征，并强调了临床前和临床研究的关键发现，说明了免疫细胞因子改善癌症患者治疗结果的潜力。还讨论了该领域的最新进展，例如增强免疫细胞因子功效和安全性的新型工程策略和组合策略。这些创新为优化此类生物治疗药物提供了新的机会，使其成为更可行、更有效的癌症治疗选择。随着该领域的不断发展，了解影响免疫细胞因子性能的关键因素对于将这些疗法成功转化为临床实践至关重要。© 2024 Prodi 等人。

Recombinant cytokine products have emerged as a promising avenue in cancer therapy due to their capacity to modulate and enhance the immune response against tumors. However, their clinical application is significantly hindered by systemic toxicities already at low doses, thus preventing escalation to therapeutically active regimens. One promising approach to overcoming these limitations is using antibody-cytokine fusion proteins (also called immunocytokines). These biopharmaceuticals leverage the targeting specificity of antibodies to deliver cytokines directly to the tumor microenvironment, thereby reducing systemic exposure and enhancing the therapeutic index. This review comprehensively examines the development and potential of antibody-cytokine fusion proteins in cancer therapy. It explores the molecular characteristics that influence the performance of these fusion proteins, and it highlights key findings from preclinical and clinical studies, illustrating the potential of immunocytokines to improve treatment outcomes in cancer patients. Recent advancements in the field, such as novel engineering strategies and combination strategies to enhance the efficacy and safety of immunocytokines, are also discussed. These innovations offer new opportunities to optimize this class of biotherapeutics, making them a more viable and effective option for cancer treatment. As the field continues to evolve, understanding the critical factors that influence the performance of immunocytokines will be essential for successfully translating these therapies into clinical practice.© 2024 Prodi et al.