Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing, China.
Department of Oncology, Nanjing Drum Tower Hospital, School of Life Science, Nanjing University, Nanjing, China.
Int Immunopharmacol. 2024 Jul 30;136:112359. doi: 10.1016/j.intimp.2024.112359. Epub 2024 May 29.
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.
白细胞介素 2（IL2）具有强有力地激活 NK 和 T 细胞的能力，但其体内半衰期有限、毒性相当大且倾向于促进 Treg 细胞，这给其在癌症治疗中的广泛应用带来了重大挑战。在本研究中，我们通过替换与 CD25 结合相关的氨基酸并进行定点 PEG 化，设计了一种新型 IL2 变体（IL2-4M-PEG），该变体具有降低的 CD25 结合活性和延长的半衰期。IL2-4M-PEG 显著扩增效应细胞而不是 Treg 细胞。此外，我们的研究结果表明，IL2-4M-PEG 具有延长的半衰期，在小鼠模型中具有抗肿瘤作用。因此，这种创新的 IL2 有可能在未来增强联合癌症治疗。
