Expansion of cytotoxic natural killer cells using irradiated autologous peripheral blood mononuclear cells and anti-CD16 antibody

Lee, Hong-Rae; Son, Cheol; Koh, Eun-Kyoung; Bae, Jae‐Ho; Kang, Chi‐Dug; Yang, Kwangmo; Park, You-Soo

doi:10.1038/s41598-017-09259-1

Cited by 46 publications

(40 citation statements)

References 61 publications

(72 reference statements)

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“…68 In vivo experiments immunising C57BL/ 6 mice with irradiated B16-F-10 melanoma (15 Gy) showed a significant accumulation of CD3 À NK1.1 + NK cells with a substantial increase in the immune regulatory NK cell subpopulation CD27 + CD11b À . 69 Another study led by Lee et al 70 examining cytotoxic NK cell expansion demonstrated that 25 Gy radiation induced upregulation of costimulatory receptors (NKG2D) critical for NK cell activation. In this study, low-dose radiotherapy of 75 mGy (12.5 mGy min À1 ) increased NK cell infiltration and induced strong cytotoxicity compared to sham irradiation.…”

Section: Increasing Natural Killer Cytotoxicitymentioning

confidence: 99%

Enhancing the efficacy of immunotherapy using radiotherapy

et al. 2020

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Recent clinical breakthroughs in cancer immunotherapy, especially with immune checkpoint blockade, offer great hope for cancer sufferersand have greatly changed the landscape of cancer treatment. However, whilst many patients achieve clinical responses, others experience minimal benefit or do not respond to immune checkpoint blockade at all. Researchers are therefore exploring multimodal approaches by combining immune checkpoint blockade with conventional cancer therapies to enhance the efficacy of treatment. A growing body of evidence from both preclinical studies and clinical observations indicates that radiotherapy could be a powerful driver to augment the efficacy of immune checkpoint blockade, because of its ability to activate the antitumor immune response and potentially overcome resistance. In this review, we describe how radiotherapy induces DNA damage and apoptosis, generates immunogenic cell death and alters the characteristics of key immune cells in the tumor microenvironment. We also discuss recent preclinical work and clinical trials combining radiotherapy and immune checkpoint blockade in thoracic and other cancers. Finally, we discuss the scheduling of immune checkpoint blockade and radiotherapy, biomarkers predicting responses to combination therapy, and how these novel data may be translated into the clinic.

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Section: Increasing Natural Killer Cytotoxicitymentioning

confidence: 99%

Enhancing the efficacy of immunotherapy using radiotherapy

et al. 2020

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“…Lee et al [92] successfully amplified a large number of the cytotoxic natural killer cells by the use of radiation irradiation of autologous peripheral blood mononuclear cells and induction of anti-CD16 monoclonal antibody. It was found that this method could effectively amplify NK cells and obtain high purity and activating NK cells with less T cell contamination.…”

Section: Nkg2d Signaling Induces High Expression Of Cd16 On Nk Cellsmentioning

confidence: 99%

Recent Advances in Molecular Mechanisms of the NKG2D Pathway in Hepatocellular Carcinoma

Wang¹,

Li²,

Sun³

2020

Biomolecules

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Hepatocellular carcinoma is a common malignant tumor with high mortality. Its malignant proliferation, invasion, and metastasis are closely related to the cellular immune function of the patients. NKG2D is a key activated and type II membrane protein molecule expressed on the surface of almost all NK cells. The human NKG2D gene is 270 kb long, located at 12p12.3–p13.1, and contains 10 exons and 9 introns. The three-dimensional structure of the NKG2D monomeric protein contains two alpha-helices, two beta-lamellae, and four disulfide bonds, and its’ signal of activation is transmitted mainly by the adaptor protein (DAP). NKG2D ligands, including MICA, MICB, and ULBPs, can be widely expressed in hepatoma cells. After a combination of NKG2D and DAP10 in the form of homologous two polymers, the YxxM motif in the cytoplasm is phosphorylated and then signaling pathways are also gradually activated, such as PI3K, PLCγ2, JNK-cJunN, and others. Activated NK cells can enhance the sensitivity to hepatoma cells and specifically dissolve by releasing a variety of cytokines (TNF-α and IFN-γ), perforin, and high expression of FasL, CD16, and TRAIL. NK cells may specifically bind to the over-expressed MICA, MICB, and ULBPs of hepatocellular carcinoma cells through the surface activating receptor NKG2D, which can help to accurately identify hepatoma, play a critical role in anti-hepatoma via the pathway of cytotoxic effects, and obviously delay the poor progress of hepatocellular carcinoma.

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“…One of the problem solving approaches is transplantation of NK cells to HCC patients, but the amount of NK cells derived from various sources is less than clinical use. Therefore, many techniques have been proposed for activation and expansion of NK cells (Cho and Campana, 2009;Ahn et al, 2013;Kamiya et al, 2016;Lee et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…In some methods, it is suggested to expansion of NK cell from whole peripheral blood lymphocytes after inhibition of T cells proliferation but some T cells may be remain after NK cell expansion (Alici et al, 2008;Fujisaki et al, 2009;Klingemann and Martinson, 2004;Peng et al, 2004). Therefore, some studies used irradiated autologous PBMC with the cytokines and mABs, as feeder layer, for NK cell expansion (Ahn et al, 2013;Lee et al, 2017). Many cytokines, have been applied for expansion and activation of NK cells such as IL-21, -18, -15, -12 and -2(Cooper et al, 2009;Romee et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Natural Killer Cell Expansion with Autologous Feeder Layer and Anti-CD3 Antibody for Immune Cell Therapy of Hepatocellular Carcinoma

Hosseinzadeh

Ebrahimi‐Barough

et al. 2019

Asian Pac J Cancer Prev

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Background: one of the promising approaches for treatment of some cancers is adoptive cell therapy using natural killer (NK) cells. Various methods have been investigated for ex vivo expansion of NK cells in large-scale, but most of them involved cancer or genetically modified cells as feeder layer and also some of them have the risk of T cell contamination and graft-versus-host disease (GVHD). Method: In this study, irradiated autologous peripheral blood mononuclear cells (PBMCs) as feeder layer with an anti-CD3 monoclonal antibody (mAb) were used. For activation and expansion of NK cells, human recombinant IL2 and IL15 were used. After co-culturing of expanded NK cells (eNKC) and isolated NK cells (iNKC) with hepatocellular carcinoma (HCC) cells, the viability of eNKC in compared to iNKC were analyzed by CCK-8 assay and degranulation of NK cells after co-culturing was assayed by measuring CD107a expression. Enzyme-Linked Immunosorbent Assay (ELISA) assay was used for the ability of NK cells to secretion of IFN-γ (interferon-γ) and TNF-α (Tumor Necrosis Factor-α) after co-culture with HCC cells. Real Time PCR analysis was used for expression of human Perforin and Granzyme B genes in the NK cells exposed to target HepG2 cells. Result: This method strongly expanded highly purified NK cells with powerful cytotoxicity against HCC cells. The expanded NK cells showed high level of expression of degranulation marker and human Perforin and Granzyme B genes, and also was secreted larger amounts of TNF-α and IFN-γ compared with fresh isolated NK cells. Conclusion: we proposed an effective method for expansion of cytotoxic NK cells using irradiated autologous PBMC as feeder layer for more successful transfer of allogeneic NK cell in immuno cell therapy of HCC.

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Expansion of cytotoxic natural killer cells using irradiated autologous peripheral blood mononuclear cells and anti-CD16 antibody

Cited by 46 publications

References 61 publications

Enhancing the efficacy of immunotherapy using radiotherapy

Enhancing the efficacy of immunotherapy using radiotherapy

Recent Advances in Molecular Mechanisms of the NKG2D Pathway in Hepatocellular Carcinoma

Natural Killer Cell Expansion with Autologous Feeder Layer and Anti-CD3 Antibody for Immune Cell Therapy of Hepatocellular Carcinoma

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