适体
嵌合抗原受体
链霉菌
CD8型
细胞毒性T细胞
寡核苷酸
生物
T细胞受体
T细胞
分子生物学
抗原
化学
细胞生物学
免疫系统
CD28
免疫学
生物化学
DNA
体外
作者
Nataly Kacherovsky,Ian I. Cardle,Emmeline L. Cheng,Jonathan L. Yu,Michael Baldwin,Stephen J. Salipante,Michael C. Jensen,Suzie H. Pun
标识
DOI:10.1038/s41551-019-0411-6
摘要
Chimeric antigen receptor T-cell therapies using defined product compositions require high-purity T-cell isolation systems that, unlike immunomagnetic positive enrichment, are inexpensive and leave no trace on the final cell product. Here, we show that DNA aptamers (generated with a modified cell−SELEX procedure to display low-nanomolar affinity for the T-cell marker CD8) enable the traceless isolation of pure CD8+ T cells at low cost and high yield. Captured CD8+ T cells are released label-free by complementary oligonucleotides that undergo toehold-mediated strand displacement with the aptamer. We also show that chimeric antigen receptor T cells manufactured from these cells are comparable to antibody-isolated chimeric antigen receptor T cells in proliferation, phenotype, effector function and antitumour activity in a mouse model of B-cell lymphoma. By employing multiple aptamers and the corresponding complementary oligonucleotides, aptamer-mediated cell selection could enable the fully synthetic, sequential and traceless isolation of desired lymphocyte subsets from a single system. DNA aptamers that specifically bind to the T-cell marker CD8 and can be displaced by a complementary oligonucleotide enable the isolation, at high purity and yield, of CD8+ T cells for chimeric antigen receptor T-cell therapies.
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