Dong Chunyan, Tan Dejiang, Sun Huimin, Li Zhuang, Zhang Linyu, Zheng Yiyang, Liu Sihan, Zhang Yu, He Qing
State Key Laboratory of Drug Regulatory Sciences, National Institutes for Food and Drug Control, Beijing 102629, China.
Curr Issues Mol Biol. 2024 Oct 16;46(10):11548-11579. doi: 10.3390/cimb46100686.
Interleukin-12 (IL-12) is considered to be a promising cytokine for enhancing an antitumor immune response; however, recombinant IL-12 has shown significant toxicity and limited efficacy in early clinical trials. Recently, many strategies for delivering IL-12 to tumor tissues have been developed, such as modifying IL-12, utilizing viral vectors, non-viral vectors, and cellular vectors. Previous studies have found that the fusion of IL-12 with extracellular matrix proteins, collagen, and immune factors is a way to enhance its therapeutic potential. In addition, studies have demonstrated that viral vectors are a good platform, and a variety of viruses such as oncolytic viruses, adenoviruses, and poxviruses have been used to deliver IL-12-with testing previously conducted in various cancer models. The local expression of IL-12 in tumors based on viral delivery avoids systemic toxicity while inducing effective antitumor immunity and acting synergistically with other therapies without compromising safety. In addition, lipid nanoparticles are currently considered to be the most mature drug delivery system. Moreover, cells are also considered to be drug carriers because they can effectively deliver therapeutic substances to tumors. In this article, we will systematically discuss the anti-tumor effects of IL-12 on its own or in combination with other therapies based on different delivery strategies.
白细胞介素-12(IL-12)被认为是一种有前景的可增强抗肿瘤免疫反应的细胞因子;然而,重组IL-12在早期临床试验中已显示出显著毒性且疗效有限。最近,已开发出许多将IL-12递送至肿瘤组织的策略,如修饰IL-12、利用病毒载体、非病毒载体和细胞载体。先前的研究发现,将IL-12与细胞外基质蛋白、胶原蛋白和免疫因子融合是增强其治疗潜力的一种方法。此外,研究表明病毒载体是一个良好的平台,多种病毒如溶瘤病毒、腺病毒和痘病毒已被用于递送IL-12——此前已在各种癌症模型中进行了测试。基于病毒递送的肿瘤局部IL-12表达可避免全身毒性,同时诱导有效的抗肿瘤免疫,并与其他疗法协同作用而不影响安全性。此外,脂质纳米颗粒目前被认为是最成熟的药物递送系统。而且,细胞也被视为药物载体,因为它们可以有效地将治疗物质递送至肿瘤。在本文中,我们将基于不同的递送策略系统地讨论IL-12单独或与其他疗法联合使用的抗肿瘤作用。
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