Multifunctional nanoparticles for genetic engineering and bioimaging of natural killer (NK) cell therapeutics

Kim, Kwangsoo; Han, Jun‐Hyeok; Park, Jung Hoon; Kim, Hyung-Keun; Choi, Seung Hee; Kim, Gyeong Ryeong; Song, Haengseok; An, Hee Jung; Han, Dong Keun; Park, Wooram; Park, Kyung-Soon

doi:10.1016/j.biomaterials.2019.119418

Cited by 58 publications

(46 citation statements)

References 45 publications

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“…In another study, biomaterial-modified Fc fragments on antibodies showed a strong potential to broaden NK cell recognition of heterogeneous antigens on solid tumors [168]. Moreover, Smit et al reported that DNA-carrying nanoparticles can efficiently introduce leukemia-targeting CAR genes into T-cells [169], which was also reported for NK-92MI cells in vitro [170]. Thus, various promising inventions from the bio-engineering field are likely to enter the CAR field as important improvements in the design and engineering of cancer immunotherapy.…”

Section: Technological Advances In Car-nk Generation: Biomaterials and In Vivo Transductionmentioning

confidence: 86%

Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy

et al. 2021

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Due to their efficient recognition and lysis of malignant cells, natural killer (NK) cells are considered as specialized immune cells that can be genetically modified to obtain capable effector cells for adoptive cellular treatment of cancer patients. However, biological and technical hurdles related to gene delivery into NK cells have dramatically restrained progress. Recent technological advancements, including improved cell expansion techniques, chimeric antigen receptors (CAR), CRISPR/Cas9 gene editing and enhanced viral transduction and electroporation, have endowed comprehensive generation and characterization of genetically modified NK cells. These promising developments assist scientists and physicians to design better applications of NK cells in clinical therapy. Notably, redirecting NK cells using CARs holds important promise for cancer immunotherapy. Various preclinical and a limited number of clinical studies using CAR-NK cells show promising results: efficient elimination of target cells without side effects, such as cytokine release syndrome and neurotoxicity which are seen in CAR-T therapies. In this review, we focus on the details of CAR-NK technology, including the design of efficient and safe CAR constructs and associated NK cell engineering techniques: the vehicles to deliver the CAR-containing transgene, detection methods for CARs, as well as NK cell sources and NK cell expansion. We summarize the current CAR-NK cell literature and include valuable lessons learned from the CAR-T cell field. This review also provides an outlook on how these approaches may transform current clinical products and protocols for cancer treatment.

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Section: Technological Advances In Car-nk Generation: Biomaterials and In Vivo Transductionmentioning

confidence: 86%

Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy

et al. 2021

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“…CAR-cell therapy is currently one of the most promising approaches for cancer treatment. Nonetheless, the development of CAR-cell therapies is challenging due to the generally low-efficient transfection of T cells and NK cells when employing lipofection reagents [ 86 ]. Magnetic nanostructures may find new applications by improving the transfection efficiency of the lymphocytes.…”

Section: Adoptive Cell Therapy For Cancer Immunotherapymentioning

confidence: 99%

“…Magnetic nanostructures may find new applications by improving the transfection efficiency of the lymphocytes. Polydopamine (PDA)-coated MNPs functionalized with polyethyleneimine (PEI), for instance, were proven to efficiently deliver genetic materials and induce the expression of EGFR targeting chimeric antigen receptors (EGFR-CARs) on the NK cell surface, which improved the cells’ anti-cancer cytotoxic effect both in vitro and in vivo [ 86 ]. The authors showed that the employed multifunctional nanoparticles did not display any significant toxicity in vitro up to a concentration of 16 µg/mL (referred as iron concentration), although at higher amounts (64 µg/mL) they displayed a 4–5 times higher cytotoxicity towards NK cells, possibly due to the increasing amount of the non-biodegradable PEI [ 86 ].…”

Section: Adoptive Cell Therapy For Cancer Immunotherapymentioning

confidence: 99%

Magnetic Nanostructures as Emerging Therapeutic Tools to Boost Anti-Tumour Immunity

Persano

Das

Pellegrino

2021

Cancers

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Cancer immunotherapy has shown remarkable results in various cancer types through a range of immunotherapeutic approaches, including chimeric antigen receptor-T cell (CAR-T) therapy, immune checkpoint blockade (ICB), and therapeutic vaccines. Despite the enormous potential of cancer immunotherapy, its application in various clinical settings has been limited by immune evasion and immune suppressive mechanisms occurring locally or systemically, low durable response rates, and severe side effects. In the last decades, the rapid advancement of nanotechnology has been aiming at the development of novel synthetic nanocarriers enabling precise and enhanced delivery of immunotherapeutics, while improving drug stability and effectiveness. Magnetic nanostructured formulations are particularly intriguing because of their easy surface functionalization, low cost, and robust manufacturing procedures, together with their suitability for the implementation of magnetically-guided and heat-based therapeutic strategies. Here, we summarize and discuss the unique features of magnetic-based nanostructures, which can be opportunely designed to potentiate classic immunotherapies, such as therapeutic vaccines, ICB, adoptive cell therapy (ACT), and in situ vaccination. Finally, we focus on how multifunctional magnetic delivery systems can facilitate the anti-tumour therapies relying on multiple immunotherapies and/or other therapeutic modalities. Combinatorial magnetic-based therapies are indeed offering the possibility to overcome current challenges in cancer immunotherapy.

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“…Nanoparticle-engineered NK cells have also been extensively investigated, including NK cells with expression of an EGFR-targeted CAR on the cell membrane realized through gene delivery and recruitment and infiltration of NK cells into tumors elevated by magnetic traction [ 65 , 66 ]. All of these approaches indicate that nanoparticles have broad applications in NK cell-mediated cancer immunotherapy.…”

Section: Nanoparticle Facilitates the Killing Ability Of Natural Killmentioning

confidence: 99%

Reversal of the immunosuppressive tumor microenvironment by nanoparticle-based activation of immune-associated cells

Wang

et al. 2020

Acta Pharmacol Sin

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Immunotherapy that activates the host immune system to reverse immunosuppression has emerged as a new generation of cancer treatment in both preclinical studies and clinical trials. Although immunotherapy has shown significant achievements in the treatment of various cancers, it faces challenges that limit its further evolution such as poor permeation and modest responsiveness. The development of nanoparticle drug delivery system has provided an opportunity to overcome these drawbacks and to achieve optimized immunotherapy. Based on the research of our group, we here introduce the new strategies being employed using nanoscale intelligent drug delivery systems to enhance the effects of cancer immunotherapy. We also provide a perspective on the further possible application of nanoparticles in more effective antitumor immunotherapy.

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Multifunctional nanoparticles for genetic engineering and bioimaging of natural killer (NK) cell therapeutics

Cited by 58 publications

References 45 publications

Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy

Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy

Magnetic Nanostructures as Emerging Therapeutic Tools to Boost Anti-Tumour Immunity

Reversal of the immunosuppressive tumor microenvironment by nanoparticle-based activation of immune-associated cells

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