Emerging nanotechnologies for cancer immunotherapy

Shukla, Sourabh; Steinmetz, Nicole F.

doi:10.1177/1535370216647123

Cited by 27 publications

(25 citation statements)

References 150 publications

(215 reference statements)

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“…Tumor-localized release of immunomodulators could potentially decrease these systemic side effects and improve the therapeutic efficacy, but is challenging. Thus, although various strategies are being explored to overcome this problem (Neri and Sondel, 2016; Shukla and Steinmetz, 2016; Tugues et al, 2015), further development is required.…”

Section: Introductionmentioning

confidence: 99%

Synthetic RNA-Based Immunomodulatory Gene Circuits for Cancer Immunotherapy

Nissim

Pery

et al. 2017

Cell

127

123

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SUMMARY Despite its success in several clinical trials, cancer immunotherapy remains limited by the rarity of targetable tumor-specific antigens, tumor-mediated immune suppression, and toxicity triggered by systemic delivery of potent immunomodulators. Here, we present a proof-of-concept immunomodulatory gene circuit platform that enables tumor-specific expression of immunostimulators, which could potentially overcome these limitations. Our design comprised de novo synthetic cancer-specific promoters and, to enhance specificity, an RNA-based AND gate that generates combinatorial immunomodulatory outputs only when both promoters are mutually active. These outputs included an immunogenic cell-surface protein, a cytokine, a chemokine, and a checkpoint inhibitor antibody. The circuits triggered selective T cell-mediated killing of cancer cells, but not of normal cells, in vitro. In in vivo efficacy assays, lentiviral circuit delivery mediated significant tumor reduction and prolonged mouse survival. Our design could be adapted to drive additional immunomodulators, sense other cancers, and potentially treat other diseases that require precise immunological programming.

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Section: Introductionmentioning

confidence: 99%

Synthetic RNA-Based Immunomodulatory Gene Circuits for Cancer Immunotherapy

Nissim

Pery

et al. 2017

Cell

127

123

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“…4 Engineered biomaterials, and in particular those that are nanostructured, 5 represent technologies that may help to overcome antigen delivery problems. 6 Nanoparticles naturally access lymphatics following immunization and interact with DCs and other APCs, 3 which may be enhanced by displaying DC-specific antibodies.…”

mentioning

confidence: 99%

Display of DNA on Nanoparticles for Targeting Antigen Presenting Cells

Molino

Neek

Tucker

et al. 2017

ACS Biomater. Sci. Eng.

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Efficient delivery of antigens is of paramount concern in immunotherapies. We aimed to target antigen presenting cells (APCs) by conjugating CpG oligonucleotides to an E2 protein nanoparticle surface (CpG-PEG-E2). Compared to E2 alone, we observed ~4-fold increase of in vitro APC uptake of both CpG-PEG-E2 and E2 conjugated to non-CpG DNA. Furthermore, compared to E2-alone or E2 functionalized solely with polyethylene glycol (PEG), the CpG-PEG-E2 showed enhanced lymph node retention up to at least 48 hr and 2-fold increase in APC uptake in vivo, parameters which are advantageous for vaccine success. This suggests that enhanced APC uptake of nanoparticles mediated by oligonucleotide display may help overcome delivery barriers in vaccine development.

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“…This is partly due to the higher requirements of immunotherapy for drug carriers, such as precise targeting, biocompatibility, and controlled release. In recent years, the researchers have put a lot of effort to develop nanotechnology-based methods to improve immunotherapy for various diseases (Look et al, 2010;Look et al, 2014;Shukla and Steinmetz, 2016;Liu et al, 2018;Al-Halifa et al, 2019). Nanomaterials-based therapeutics with unique properties may help address some of the key technical challenges in immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

DNA Nanostructure as an Efficient Drug Delivery Platform for Immunotherapy

Chi

Yang

et al. 2020

Front. Pharmacol.

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Immunotherapy has received increasing attention due to its low potential side effects and high specificity. For instance, cancer immunotherapy has achieved great success. CpG is a well-known and commonly used immunotherapeutic and vaccine adjuvant, but it has the disadvantage of being unstable and low in efficacy and needs to be transported through an effective nanocarrier. With perfect structural programmability, permeability, and biocompatibility, DNA nanostructures are one of the most promising candidates to deliver immune components to realize immunotherapy. However, the instability and low capability of the payload of ordinary DNA assemblies limit the relevant applications. Consequently, DNA nanostructure with a firm structure, high drug payloads is highly desirable. In the paper, the latest progress of biostable, high-payload DNA nanoassemblies of various structures, including cage-like DNA nanostructure, DNA particles, DNA polypods, and DNA hydrogel, are reviewed. Cage-like DNA structures hold drug molecules firmly inside the structure and leave a large space within the cavity. These DNA nanostructures use their unique structure to carry abundant CpG, and their biocompatibility and size advantages to enter immune cells to achieve immunotherapy for various diseases. Part of the DNA nanostructures can also achieve more effective treatment in conjunction with other functional components such as aPD1, RNA, TLR ligands.

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Emerging nanotechnologies for cancer immunotherapy

Cited by 27 publications

References 150 publications

Synthetic RNA-Based Immunomodulatory Gene Circuits for Cancer Immunotherapy

Synthetic RNA-Based Immunomodulatory Gene Circuits for Cancer Immunotherapy

Display of DNA on Nanoparticles for Targeting Antigen Presenting Cells

DNA Nanostructure as an Efficient Drug Delivery Platform for Immunotherapy

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