设计含锚蛋白重复序列蛋白作为嵌合抗原受体修饰 T 细胞的 Her2 靶向结构域。
Designed Ankyrin Repeat Proteins as Her2 Targeting Domains in Chimeric Antigen Receptor-Engineered T Cells.
机构信息
1 Department of Biomedical Engineering, University of Southern California , Los Angeles, California.
2 Department of Pharmacology and Pharmaceutical Sciences, University of Southern California , Los Angeles, California.
出版信息
Hum Gene Ther. 2017 Sep;28(9):726-736. doi: 10.1089/hum.2017.021. Epub 2017 Jun 22.
Chimeric antigen receptor (CAR) engineering is a branch of cancer immunotherapy that equips immune cells to target tumor antigens expressed on the cell surface using antibody-derived single-chain variable fragments (scFvs). However, other antibody mimetics, such as designed ankyrin repeat proteins (DARPins), can also serve as antigen-binding domains in CARs. This study shows that CAR-engineered T (CAR-T) cells utilizing Her2-targeting DARPins G3 and 929 can target human epidermal growth factor receptor 2 (Her2)-overexpressing cancer cells as effectively as CAR-T cells with the scFv 4D5 in vitro, and G3 CAR-T cells can slow or eliminate tumor growth in vivo as effectively as 4D5 CAR-T cells. Some DARPins may offer an attractive alternative to scFv usage in CARs, as they are smaller, thermodynamically stable, poorly immunogenic, and can be generated with different binding properties from DARPin libraries.
嵌合抗原受体 (CAR) 工程是癌症免疫疗法的一个分支，它使用源自抗体的单链可变片段 (scFv) 使免疫细胞能够靶向细胞表面表达的肿瘤抗原。然而，其他抗体模拟物，如设计的锚蛋白重复蛋白 (DARPins)，也可以作为 CAR 中的抗原结合结构域。本研究表明，利用 Her2 靶向 DARPin G3 和 929 构建的 CAR-T 细胞在体外可以像使用 scFv 4D5 的 CAR-T 细胞一样有效地靶向人表皮生长因子受体 2 (Her2) 过表达的癌细胞，并且 G3 CAR-T 细胞在体内可以像 4D5 CAR-T 细胞一样有效地减缓或消除肿瘤生长。一些 DARPins 在 CAR 中可能是 scFv 的一种有吸引力的替代物，因为它们更小、热力学稳定、免疫原性差，并且可以从 DARPin 文库中产生具有不同结合特性的 DARPins。
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