Natural Killer Cells for Immunotherapy – Advantages of the NK-92 Cell Line over Blood NK Cells

Klingemann, Hans; Boissel, Laurent; Toneguzzo, Frances

doi:10.3389/fimmu.2016.00091

Cited by 330 publications

(355 citation statements)

References 47 publications

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“…The YSK12-MEND can be a helpful technology for gene functional analysis. NK92 cells have been used for NK-based cancer immune therapy in clinical trials29. Although some problems remain, the YSK12-MEND may be applicable for use in NK-based cancer immune therapy in the future.…”

Section: Discussionmentioning

confidence: 99%

Small-sized, stable lipid nanoparticle for the efficient delivery of siRNA to human immune cell lines

Nakamura

Kuroi

Fujiwara

et al. 2016

Sci Rep

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Gene silencing by small interfering RNA (siRNA) is useful for analyzing the functions of human immune cells. However, the transfection of siRNA to human immune cells is difficult. Here, we used a multifunctional envelope-type nanodevice (MEND) containing YSK12-C4 (YSK12-MEND) to efficiently introduce siRNA to human immune cell lines, Jurkat, THP-1, KG-1 and NK92. The YSK12-MEND was transfected to human immune cell lines at a siRNA dose range of 1–30 nM, resulting that maximum gene silencing efficiencies at the mRNA level in Jurkat, THP-1, KG-1 and NK92 were 96%, 96%, 91% and 75%, respectively. The corresponding values for Lipofectamine RNAiMAX (RNAiMAX) were 37%, 56%, 43% and 19%, respectively. The process associated with cellular uptake played a role in effective gene silencing effect of the YSK12-MEND. The small size and high non-aggregability of the YSK12-MEND were advantageous for the cellular internalization of siRNA to immune cell lines. In the case of RNAiMAX, a drastic increase in particles size was observed in the medium used, which inhibited cellular uptake. The YSK12-MEND reported in herein appears to be appropriate for delivering siRNA to human immune cells, and the small particle size and non-aggregability are essential properties.

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Section: Discussionmentioning

confidence: 99%

Small-sized, stable lipid nanoparticle for the efficient delivery of siRNA to human immune cell lines

Nakamura

Kuroi

Fujiwara

et al. 2016

Sci Rep

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“…Methodology for continuous good manufacturing practice (GMP)-compliant expansion from an established master cell bank has been validated in the framework of early phase clinical trials with unmodified NK-92 cells and can easily be adapted for large-scale production in centralized facilities (32, 90). This advantage may readily be extended to CAR-engineered NK-92 variants.…”

Section: Continuous Expansion Of Car Nk-92 Cellsmentioning

confidence: 99%

“…NK-92, which is phenotypically CD16-negative, readily mediates ADCC in the presence of a suitable IgG antibody when engineered to express FcγRIIIa (27, 97, 100). This has sparked efforts to clinically develop genetically modified NK-92 cells that harbor the high affinity V158 variant of CD16 (termed haNK) in combination with antibodies of IgG1 isotype (32, 97). Initial safety assessment of such cells in cancer patients is expected to begin soon (NCT03027128; ).…”

Section: Car-engineered Nk-92 Cells Exhibit Antibody-dependent Cell-mmentioning

confidence: 99%

“…Other inhibitory receptors expressed by NK-92 are Ig-like transcript 2 (ILT-2) and NKG2A/CD94. This unique profile renders NK-92 cells highly cytotoxic against a broad spectrum of malignant cells of hematologic origin and other cancers (32). General safety of infusion of irradiated NK-92 cells has been established in phase I clinical trials in patients with advanced cancers (35, 36), and results from other phase I and phase II studies may soon become available (NCT00990717, NCT00900809, NCT02465957; ).…”

Section: Introductionmentioning

confidence: 99%

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Chimeric Antigen Receptor-Engineered NK-92 Cells: An Off-the-Shelf Cellular Therapeutic for Targeted Elimination of Cancer Cells and Induction of Protective Antitumor Immunity

et al. 2017

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Significant progress has been made in recent years toward realizing the potential of natural killer (NK) cells for cancer immunotherapy. NK cells can respond rapidly to transformed and stressed cells and have the intrinsic potential to extravasate and reach their targets in almost all body tissues. In addition to donor-derived primary NK cells, also the established NK cell line NK-92 is being developed for adoptive immunotherapy, and general safety of infusion of irradiated NK-92 cells has been established in phase I clinical trials with clinical responses observed in some of the cancer patients treated. To enhance their therapeutic utility, NK-92 cells have been modified to express chimeric antigen receptors (CARs) composed of a tumor-specific single chain fragment variable antibody fragment fused via hinge and transmembrane regions to intracellular signaling moieties such as CD3ζ or composite signaling domains containing a costimulatory protein together with CD3ζ. CAR-mediated activation of NK cells then bypasses inhibitory signals and overcomes NK resistance of tumor cells. In contrast to primary NK cells, CAR-engineered NK-92 cell lines suitable for clinical development can be established from molecularly and functionally well-characterized single cell clones following good manufacturing practice-compliant procedures. In preclinical in vitro and in vivo models, potent antitumor activity of NK-92 variants targeted to differentiation antigens expressed by hematologic malignancies, and overexpressed or mutated self-antigens associated with solid tumors has been found, encouraging further development of CAR-engineered NK-92 cells. Importantly, in syngeneic mouse tumor models, induction of endogenous antitumor immunity after treatment with CAR-expressing NK-92 cells has been demonstrated, resulting in cures and long-lasting immunological memory protecting against tumor rechallenge at distant sites. Here, we summarize the current status and future prospects of CAR-engineered NK-92 cells as off-the-shelf cellular therapeutics, with special emphasis on ErbB2 (HER2)-specific NK-92 cells that are approaching clinical application.

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“…Consequently, these effector cells are unable to recognise tumour-targeted antigens by ADCC mechanisms. To overcome these cytotoxic limitations, NK-92 cells were genetically manipulated to express the high-affinity V158 variant of the Fc-gamma receptor (FcγRIIIa/CD16a, termed haNK TM ) and to produce endogenous, intracellularly retained IL-2 [95, 96]. In an ongoing phase I trial it will be evaluated whether infused haNK TM cells are safe and potent in the treatment of patients with histologically confirmed, non-resectable, and locally advanced or metastatic solid tumours (NCT03027128; https://clinicaltrials.gov; Table 1).…”

Section: Car-expressing Nk-92 Cells For Retargeting Of Solid Tumoursmentioning

confidence: 99%

CAR-Expressing Natural Killer Cells for Cancer Retargeting

Kloeß

Kretschmer

Stahl

et al. 2019

Transfus Med Hemother

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Since the approval in 2017 and the outstanding success of Kymriah® and Yescarta®, the number of clinical trials investigating the safety and efficacy of chimeric antigen receptor-modified autologous T cells has been constantly rising. Currently, more than 200 clinical trials are listed on clinicaltrial.gov. In contrast to CAR-T cells, natural killer (NK) cells can be used from allogeneic donors as an “off the shelf product” and provide alternative candidates for cancer retargeting. This review summarises preclinical results of CAR-engineered NK cells using both primary human NK cells and the cell line NK-92, and provides an overview about the first clinical CAR-NK cell studies targeting haematological malignancies and solid tumours, respectively.

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Natural Killer Cells for Immunotherapy – Advantages of the NK-92 Cell Line over Blood NK Cells

Cited by 330 publications

References 47 publications

Small-sized, stable lipid nanoparticle for the efficient delivery of siRNA to human immune cell lines

Small-sized, stable lipid nanoparticle for the efficient delivery of siRNA to human immune cell lines

Chimeric Antigen Receptor-Engineered NK-92 Cells: An Off-the-Shelf Cellular Therapeutic for Targeted Elimination of Cancer Cells and Induction of Protective Antitumor Immunity

CAR-Expressing Natural Killer Cells for Cancer Retargeting

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