Current landscape and future prospects of interleukin-2 receptor (IL-2R) agonists in cancer immunotherapy.
Publication Title
Oncoimmunology
Document Type
Article
Publication Date
12-1-2025
Keywords
Humans; Immunotherapy; Interleukin-2; Neoplasms; Receptors, Interleukin-2; Lymphocytes, Tumor-Infiltrating; Animals; Cancer; High-dose IL-2 (HD IL-2); IL-2 receptor (IL-2R); IL-2R agonist; Interleukin-2 (IL-2); clinical trials; cytokine; immunotherapy; oregon; portland; chiles
Abstract
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.
Area of Special Interest
Cancer
Specialty/Research Institute
Oncology
Specialty/Research Institute
Pulmonary Medicine
DOI
10.1080/2162402X.2025.2452654
