A homodimeric IL-15 superagonist F4RLI with easy preparation, improved half-life, and potent antitumor activities
Autor: | Liangyin Lv, Hui Wang, Wenqiang Shi, Yang Wang, Wen Zhu, Zexin Liu, Xiaoqu Chen, Chen Zheng, Wencheng Kong, Wei Li, Jianwei Zhu, Huili Lu |
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Rok vydání: | 2022 |
Předmět: |
Interleukin-15
Biological Products Programmed Cell Death 1 Receptor Angiogenesis Inhibitors Antineoplastic Agents General Medicine CD8-Positive T-Lymphocytes Applied Microbiology and Biotechnology B7-H1 Antigen Immunoglobulin Fc Fragments Bevacizumab Mice Cell Line Tumor Immunoglobulin G Animals Humans Immunotherapy Immune Checkpoint Inhibitors Half-Life Biotechnology |
Zdroj: | Applied Microbiology and Biotechnology. 106:7039-7050 |
ISSN: | 1432-0614 0175-7598 |
DOI: | 10.1007/s00253-022-12209-1 |
Popis: | Interleukin-15 (IL-15) is a promising candidate for cancer immunotherapy due to its potent immune-activating effects. There are several IL-15 molecules currently in clinical trials but facing shortages of poor half-life, circulation instability, or complicated production and quality control processes. The aim of this study is to design a novel IL-15 superagonist to set out the above difficulties, and we constructed F4RLI consisting of the GS-linker spaced IgG4 Fc fragment, soluble IL-15 Rα (sIL-15Rα), and IL-15(N72D). Using a single plasmid transient transfection in HEK293E cells, the matured F4RLI was secreted in the form of homodimer and got purified by an easy step of protein A affinity chromatography. The F4RLI product can significantly stimulate the proliferation of human CD3 |
Databáze: | OpenAIRE |
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