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白细胞介素-2 受体(IL-2R)激动剂在肿瘤免疫治疗中的现状与未来前景

英文原题:Current landscape and future prospects of interleukin-2 receptor (IL-2R) agonists in cancer immunotherapy.

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Current landscape and future prospects of interleukin-2 receptor (IL-2R) agonists in cancer immunotherapy.

PubMed 2025/01/15(内容时间) Oncoimmunology Q1 · IF 6.2(JCR 2025)

研究概要

然而,不到50%的患者从ICB中获益,这凸显了对更有效免疫治疗选择的需求。

中文摘要

免疫检查点阻断(ICB)已显著改善了许多晚期恶性肿瘤患者的生存。然而,不足50%的患者从ICB中获益,这凸显了对更有效免疫治疗选择的需求。高剂量白细胞介素-2(HD IL-2)免疫治疗已获批用于转移性黑色素瘤和肾细胞癌患者,可刺激CD8+ T细胞和NK细胞,并可在部分患者中产生持久缓解。此外,HD IL-2可能对ICB后疾病进展的患者具有潜在疗效,并在TIL治疗中扩增TIL(肿瘤浸润淋巴细胞)方面发挥重要作用。尽管具有潜力,HD IL-2的使用受到严重毒性(如低血压和血管渗漏综合征)的限制。此外,只有少数患者在HD IL-2治疗后获得良好结局。为应对这些挑战,已开发出众多下一代IL-2受体(IL-2 R)激动剂,以在发挥治疗效果的同时尽量减少不良事件。本综述将探讨IL-2生物学、HD IL-2治疗的临床应用,以及用于癌症免疫治疗的新型IL-2 R激动剂的开发。

展开英文摘要原文

Immune checkpoint blockade (ICB) has significantly improved the survival for many patients with advanced malignancy. However, fewer than 50% of patients benefit from ICB, highlighting the need for more effective immunotherapy options. High-dose interleukin-2 (HD IL-2) immunotherapy, which is approved for patients with metastatic melanoma and renal cell carcinoma, stimulates CD8 + T cells and NK cells and can generate durable responses in a subset of patients. Moreover, HD IL-2 may have potential efficacy in patients whose disease has progressed following ICB and plays a vital role in expanding tumor-infiltrating lymphocyte (TIL) in TIL therapy. Despite its potential, the use of HD IL-2 is limited by severe toxicities such as hypotension and vascular leak syndrome. Additionally, only a few patients achieve a good outcome after HD IL-2 therapy. To address these challenges, numerous next-generation IL-2 receptor (IL-2 R) agonists have been developed to exhibit treatment effects while minimizing adverse events. This review will explore IL-2 biology, the clinical application of HD IL-2 therapy, and the development of novel IL-2 R agonists for cancer immunotherapy.

论文信息

作者
Tanigawa K、Redmond WL
单位
Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA.United States
文献类型
综述
期刊
Oncoimmunology2025 Dec
原文标识
PubMed 39812092 · DOI 10.1080/2162402X.2025.2452654