1. Site-specific pegylated IL2 mutein with biased IL2 receptor binding for cancer immunotherapy.
- Author
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Tong, Bei, Leong, Sirou Grace, Jian, Tunyu, Niu, Guanting, Gai, Yanan, Meng, Xiuhua, Lv, Han, Dong, Xianchi, Ding, Xiaoqin, and Chen, Jian
- Subjects
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REGULATORY T cells , *T cells , *IMMUNOTHERAPY , *KILLER cells , *CANCER treatment , *CD25 antigen - Abstract
• PEGylation is advantageous for extending the in vivo half-life of IL2. • Constructing IL2 mutant to impart a bias towards inducing effector T cells. • EC50 ratio of Mo7e and CTLL-2 cells is an indicator for immunotherapy evaluation. While Interleukin 2 (IL2) has the capability to activate both NK and T cells robustly, its limited in vivo half-life, considerable toxicity, and tendency to boost Treg cells pose significant challenges, restricting its widespread application in cancer therapy. In this investigation, we engineered a novel IL2 variant (IL2-4M-PEG) with reduced CD25 binding activity and an extended half-life by substituting amino acids associated with CD25 binding and implementing site-directed PEGylation. IL2-4M-PEG notably amplifies effector cells over Treg cells. Furthermore, our findings reveal that IL2-4M-PEG, characterized by an extended half-life, exhibits anti-tumor effects in a mouse model. Consequently, this innovative IL2 holds the potential for enhancing combined cancer therapies in the future. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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