文章基本信息

标题：Discovery of a novel IL-15 based protein with improved developability and efficacy for cancer immunotherapy
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作者：Qiyue Hu ; Xin Ye ; Xiangdong Qu 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2018
卷号：8
期号：1
页码：7675
DOI：10.1038/s41598-018-25987-4
语种：English
出版社：Springer Nature
摘要：T cells and natural killer cells (NK) while showing no effect in activating T-regulatory (Treg) cells or inducing activation-associated death among effector T cells and NK cells. Thus, IL-15 is considered as one of the most promising molecules for antitumor immune therapy. To improve the drug-like properties of natural IL-15, we create an IL-15-based molecule, named P22339, with the following characteristics: 1) building a complex of IL-15 and the Sushi domain of IL-15 receptor α chain to enhance the agonist activity of IL-15 via transpresentation; 2) through a rational structure-based design, creating a disulfide bond linking the IL-15/Sushi domain complex with an IgG1 Fc to augment its half-life. P22339 demonstrates excellent developability, pharmacokinetic and pharmacodynamic properties as well as antitumor efficacy in both in vitro assessments and in vivo studies. It significantly suppresses tumor growth and metastasis in rodent models, and activates T effector cells and NK cells in cynomolgus monkey. Overall, these data suggest that P22339 has a great potential for cancer immunotherapy.