In situ programming of leukaemia-specific T cells using synthetic DNA nanocarriers

Smith, Tyrel T.; Stephan, Sirkka B.; Moffett, Howell F.; McKnight, Laura E.; Ji, Weihang; Reiman, Diana; Bonagofski, Emmy; Wohlfahrt, Martin E.; Pillai, Smitha P.S.; Stephan, Matthias T.

doi:10.1038/nnano.2017.57

Cited by 580 publications

(535 citation statements)

References 31 publications

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“…The ongoing development of nanoparticles not only improves the targeting and bioavailability of drugs and develops new therapeutic methods, such as photothermal therapy and nanovaccines, but also provides a suitable carrier for the realization of combination therapy 2, 3, 4, 5, 6, 7. Moreover, some nanoparticle‐based systems can strengthen the immune response in tumor immunotherapy, which has attracted much attention 8, 9, 10, 11…”

Section: Introductionmentioning

confidence: 99%

Photosensitizer Micelles Together with IDO Inhibitor Enhance Cancer Photothermal Therapy and Immunotherapy

et al. 2018

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The therapeutic outcome of photothermal therapy (PTT) remains impeded by the transparent depth of light. Combining PTT with immunotherapy provides strategies to solve this problem. Regulating metabolism‐related enzymes is a promising strategy to stimulate immune response. Here, a nanosystem (NLG919/IR780 micelles) with the properties of photothermal conversion and regulation of the tryptophan metabolic pathway is used to suppress the growth of the tumor margin beyond effective PTT and promote tumor PTT and immunotherapy. It is revealed that mild heat treatment promotes the growth of the tumor margin beyond effective PTT for the upregulation of heat shock protein (HSP), indoleamine 2,3‐dioxygenase (IDO), and programmed death‐ligand 1 (PD‐L1). The NLG919/IR780 micelles can effectively inhibit the activity of IDO but do not affect the level of IDO expression. NLG919/IR780 micelles can effectively accumulate in the tumor and can migrate to lymph nodes and the lymphatic system. In vivo antitumor studies reveal that NLG919/IR780 micelles effectively suppress the growth of tumor margin following PTT in primary tumors. NLG919/IR780 micelle‐mediated PTT and IDO inhibition further stimulate the activation of T lymphocytes, inhibiting the growth of distal tumors (abscopal effect). The results demonstrate that the NLG919/IR780 micelles combine PTT and immunotherapy and suppress the tumor margin as well as distal tumor growth post photothermal therapy.

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Section: Introductionmentioning

confidence: 99%

Photosensitizer Micelles Together with IDO Inhibitor Enhance Cancer Photothermal Therapy and Immunotherapy

et al. 2018

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“…When they infused these agents into mice, the nanoparticles moved into lymph nodes, where the cargo was released, allowing the new genes to be incorporated in the T cells. Seven out of 10 mice showed complete tumor eradication, results that were nearly comparable to treatment with externally reprogrammed T cells (4). …”

Section: Reprogramming T Cellsmentioning

confidence: 89%

Injecting Nanoparticles into Immunotherapy

Webb¹

2017

BioTechniques

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“…167 Recently, in vivo administration of nanoparticles carrying transposons has emerged as an efficient method to deliver transgenes into circulating T cells in mice, and in situ engineered T cells exhibited similar activity to conventional engineered T cells generated by ex vivo gene transfer. 168 Nanoparticles represents a potentially attractive technology to deliver transposons into liver sinusoidal endothelial cells. 169 Intramuscular electroporation of transposons in murine models resulted in transient and localized transgene expression.…”

Section: Hscmentioning

confidence: 99%

Transposons: Moving Forward from Preclinical Studies to Clinical Trials

Tipanee¹,

VandenDriessche

Chuah

2017

Human Gene Therapy

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Transposons have emerged as promising vectors for gene therapy that can potentially overcome some of the limitations of commonly used viral vectors. Transposons stably integrate into the target cell genome, enabling persistent expression of therapeutic genes. Transposons have evolved from being used as basic tools in biomedical research to bona fide therapeutics. Currently, the most promising transposons for gene therapy applications are derived from Sleeping Beauty (SB) or piggyBac (PB). Stable transposition requires co-delivery of the transposon DNA with the corresponding transposase gene, mRNA, or protein. Stable transposition efficiency can be substantially increased by using "next-generation" transposon systems that combine codon-usage optimization with hyper-activating mutations in the SB or PB transposases. By virtue of their relatively large capacity, gene therapy applications with relatively large therapeutic transgenes, such as full-length dystrophin, can now be envisaged. The authors and others have shown that efficient and stable gene transfer can be achieved with these next-generation transposons in several clinically relevant primary cells, such as CD34 hematopoietic stem/progenitor cells, T cells, and mesenchymal and myogenic stem/progenitor cells that are amenable for ex vivo transfection. Alternatively, in vivo transposon gene delivery has been explored using non-viral vectors or nanoparticles or in combination with viral vectors. The therapeutic potential of these SB- and PB-based transposons has been demonstrated in preclinical models that mimic the cognate human diseases. However, there are still challenges impeding clinical translation of transposons pertaining mainly to the typical limiting efficiencies of most non-viral transfection methods and the intrinsic DNA toxicity. Nevertheless, it is particularly encouraging that transposons have now been used in gene therapy clinical trials. In particular, transposon-engineered T cells expressing chimeric antigen receptors are starting to yield promising results in patients with hematological malignancies.

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In situ programming of leukaemia-specific T cells using synthetic DNA nanocarriers

Cited by 580 publications

References 31 publications

Photosensitizer Micelles Together with IDO Inhibitor Enhance Cancer Photothermal Therapy and Immunotherapy

Photosensitizer Micelles Together with IDO Inhibitor Enhance Cancer Photothermal Therapy and Immunotherapy

Injecting Nanoparticles into Immunotherapy

Transposons: Moving Forward from Preclinical Studies to Clinical Trials

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