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Traceless isolation of killer T cells via DNA aptamers

Traceless aptamer-mediated isolation of CD8+ T cells for chimeric antigen receptor T-cell therapy

This issue highlights an overview of immunotherapies leveraging engineering approaches, the traceless isolation of CD8+ T cells for CAR-T cell therapy, high-throughput immunomagnetic cell sorting implemented in a microfluidic chip, orthologous therapeutic proteins that elude the adaptive immune system, glycosylated peptides for preventing T-cell-mediated diabetes in mice, and a cell-culture system for assembling 3D tissue models by stacking layers containing pre-conditioned microenvironments.

The cover illustrates the isolation of CD8+ T cells by magnetic microbeads functionalized with DNA aptamers that specifically bind to the T-cell marker CD8 and that can be displaced by a complementary oligonucleotide.

Abstract: 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.


Nature Biomedical Engineering volume 3pages783–795 (2019)



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