Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Republic of Korea.
Laboratory of Host Defenses, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; KAIST Institute of Health Science and Technology, KAIST, Daejeon 34141, Republic of Korea.
Biomed Pharmacother. 2024 Oct;179:117426. doi: 10.1016/j.biopha.2024.117426. Epub 2024 Sep 8.
Interferons are a family of cytokines that are famously known for their involvement in innate and adaptive immunity. Type I interferons (IFNs) exert pleiotropic effects on various immune cells and contribute to tumor-intrinsic and extrinsic mechanisms. Their pleiotropic effects and ubiquitous expression on nucleated cells have made them attractive candidates for cytokine engineering to deliver to largely immunosuppressive tumors. Type III interferons were believed to play overlapping roles with type I IFNs because they share a similar signaling pathway and induce similar transcriptional programs. However, type III IFNs are unique in their cell specific receptor expression and their antitumor activity is specific to a narrow range of cell types. Thus, type III IFN based therapies may show reduced toxic side effects compared with type I IFN based treatment. In this review, we focus on the development of IFN-based therapeutics used to treat different tumors. We highlight how the development in cytokine engineering has allowed for efficient delivery of type I and type III IFNs to tumor sites and look ahead to the obstacles that are still associated with IFN-based therapies before they can be fully and safely integrated into clinical settings.
干扰素是细胞因子家族的一员，以其参与固有和适应性免疫而闻名。I 型干扰素（IFN）对各种免疫细胞发挥多效作用，并有助于肿瘤内在和外在机制。它们在有核细胞上的多效性表达和广泛表达使它们成为细胞因子工程的有吸引力的候选物，可将其递送至广泛免疫抑制的肿瘤。III 型干扰素被认为与 I 型 IFNs 发挥重叠作用，因为它们共享相似的信号通路并诱导相似的转录程序。然而，III 型 IFNs 在其细胞特异性受体表达上是独特的，其抗肿瘤活性仅限于狭窄的细胞类型。因此，与基于 I 型 IFN 的治疗相比，基于 III 型 IFN 的治疗可能显示出降低的毒副作用。在这篇综述中，我们专注于基于 IFN 的治疗剂的开发，用于治疗不同的肿瘤。我们强调了细胞因子工程的发展如何允许将 I 型和 III 型 IFNs 有效地递送至肿瘤部位，并展望在 IFN 治疗完全和安全地整合到临床环境之前仍然存在的障碍。
