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Traceless isolation of killer T cells via DNA aptamers
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.
For genome-wide screens and other applications that require the processing of a large number of cells, the immunomagnetic sorting of cells on a microfluidic chip is a scalable, rapid and cost-efficient alternative to fluorescence-activated cell sorting.
Targeting antigens to the liver by glycosylation promotes antigen-specific immune tolerance via the expansion of regulatory T cells and prevents autoimmunity in a mouse model of type-1 diabetes.
In mouse models of cancer, the inhibition of a set of regulatory proteins improves checkpoint-blockade therapy by causing regulatory T cells to produce the cytokine interferon-γ.
This Perspective overviews immunotherapies leveraging engineering approaches, including the design of biomaterials, delivery strategies and nanotechnology solutions, for the realization of individualized cancer treatments.
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.
Immunomagnetic cell sorting implemented in a microfluidic chip can perform loss-of-function CRISPR–Cas9-mediated phenotypic screening at higher throughput than fluorescence-activated cell sorting.
Orthologous therapeutic proteins can elude the adaptive immune system and allow for effective repeated dosing, as shown for CRISPR gene editing with orthologues of adeno-associated viral capsids and of the Cas9 protein.
A reconfigurable microfluidic cell-culture system that facilitates the assembly of 3D tissue models by stacking layers containing preconditioned microenvironments enables the modelling of the spatiotemporal dynamics of paracrine signalling.