<i>Ex Vivo</i> Activation of CD56+ Immune Cells That Eradicate Neuroblastoma

Rujkijyanont, Piya; Chan, Wing Keung; Eldridge, Paul W.; Lockey, Timothy; Holladay, Martha; Rooney, Barbara; Davidoff, Andrew M.; Leung, Wing; Vong, Queenie

doi:10.1158/0008-5472.can-12-3322

Cited by 24 publications

(21 citation statements)

References 37 publications

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“…NCAM1, also known as CD56 is part of the immunoglobulin superfamily and is expressed on the surface of neural cells [23] and certain cells of the immune system [24]. NCAM1 is classically known as a cell surface molecule and cell adhesion in neuronal cells.…”

Section: Discussionmentioning

confidence: 99%

Loss of expression of the Neural Cell Adhesion Molecule 1 (NCAM1) in atypical teratoid/rhabdoid tumors: a new diagnostic marker?

Suzuki

Patel²,

Huang

et al. 2017

Appl Cancer Res

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Background: Atypical teratoid/rhabdoid tumors (AT/RT) are aggressive embryonal tumors of the central nervous system. They are largely characterized by inactivating mutations of the SMARCB1 tumor suppressor gene. AT/RT patients have a very poor prognosis and no standard therapeutic protocol has been defined yet. Recently, multimodal therapy with multiple drug combinations has slightly improved the overall survival, however drug toxicity remains high. In this scenario, a better understanding of the pathophysiology of the disease is needed.

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Section: Discussionmentioning

confidence: 99%

Loss of expression of the Neural Cell Adhesion Molecule 1 (NCAM1) in atypical teratoid/rhabdoid tumors: a new diagnostic marker?

Suzuki

Patel²,

Huang

et al. 2017

Appl Cancer Res

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“…Some preclinical studies have shown that NK cell infusion has good efficacy as an immunotherapy for NB [26]. However, NK cells express a complicated range of receptors, such as inhibitory and activating receptors, and their binding to different ligands may affect the efficacy of immunotherapy in NB [27].…”

Section: Discussionmentioning

confidence: 99%

Involvement of IL-10 and TGF-β in HLA-E-mediated neuroblastoma migration and invasion

et al. 2016

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Human leukocyte antigen (HLA)-E is highly expressed in a variety of tumors and, in addition to immune escape, may promote tumor growth via other mechanisms. However, the role of HLA-E in neuroblastoma (NB) migration and invasion is unknown. In the present study, HLA-E expression in human NB tumors was measured by immunohistochemistry. The effect of HLA-E on NB cell migration and invasion was studied in vitro and in vivo, as well as the effect of HLA-E on natural killer (NK)-cell cytotoxicity. HLA-E was expressed in 70.2% of the NB tumor tissues examined. HLA-E expression by NB cells inhibited NK-cell cytotoxicity and induced the release of interleukin (IL)-10 and transforming growth factor (TGF)-β1. HLA-E and the released cytokines enhanced the ability of NB cells migration and invasion. NK cell infusion did not inhibit the growth of NB cells with high HLA-E expression but instead increased the number of metastatic cells in the bone marrow. Taken together, the results indicate that IL-10 and TGF-β are involved in HLA-E-mediated NB migration and invasion. Thus, HLA-E may be a new treatment target in NB.

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“…Starting with PBMC enriched for CD56 cells together with the corresponding non-CD56 PBMC in a 1:1 mixture favors a 89-fold NK cell expansion with a final product consisting of 92% NK cells after 21 days (69). Alternatively, adding irradiated autologous PBMC to the culture is a strategy to benefit from these “feeder cells” for NK cell activation and expansion but to avoid their coexpansion (Table 3).…”

Section: Autologous Accessory Cells and Autologous Feeder Cells For Nmentioning

confidence: 99%

“…A first feasibility study of automated NK cell cultivation with a stirred bioreactor was already published in 1996, showing advantages of the bioreactor culture over manually handled controls (159). More recently, different investigators report automated NK cell expansion procedures with a rocking motion bioreactor (67, 69, 156, 160), yielding 2–10 × 10 9 NK cells under GMP-compliant conditions. However, the latter system still needs preceding manual cultivation, because relatively high cell numbers are required as inoculum for the automated culture (67, 69, 156, 160).…”

Section: Technical Aspects Of Nk Cell Expansionmentioning

confidence: 99%

“…More recently, different investigators report automated NK cell expansion procedures with a rocking motion bioreactor (67, 69, 156, 160), yielding 2–10 × 10 9 NK cells under GMP-compliant conditions. However, the latter system still needs preceding manual cultivation, because relatively high cell numbers are required as inoculum for the automated culture (67, 69, 156, 160). Alternatively, fully automated NK cell expansion with an automated cell processing device can be performed for clinical use, with as little as 10 6 NK cells being sufficient to initiate the automated culture that can yield up to 2.7 × 10 9 NK cells after stimulation with clinical grade feeder cells (142).…”

Section: Technical Aspects Of Nk Cell Expansionmentioning

confidence: 99%

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Shaping of Natural Killer Cell Antitumor Activity by Ex Vivo Cultivation

Granzin¹,

et al. 2017

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Natural killer (NK) cells are a promising tool for the use in adoptive immunotherapy, since they efficiently recognize and kill tumor cells. In this context, ex vivo cultivation is an attractive option to increase NK cells in numbers and to improve their antitumor potential prior to clinical applications. Consequently, various strategies to generate NK cells for adoptive immunotherapy have been developed. Here, we give an overview of different NK cell cultivation approaches and their impact on shaping the NK cell antitumor activity. So far, the cytokines interleukin (IL)-2, IL-12, IL-15, IL-18, and IL-21 are used to culture and expand NK cells. The selection of the respective cytokine combination is an important factor that directly affects NK cell maturation, proliferation, survival, distribution of NK cell subpopulations, activation, and function in terms of cytokine production and cytotoxic potential. Importantly, cytokines can upregulate the expression of certain activating receptors on NK cells, thereby increasing their responsiveness against tumor cells that express the corresponding ligands. Apart from using cytokines, cocultivation with autologous accessory non-NK cells or addition of growth-inactivated feeder cells are approaches for NK cell cultivation with pronounced effects on NK cell activation and expansion. Furthermore, ex vivo cultivation was reported to prime NK cells for the killing of tumor cells that were previously resistant to NK cell attack. In general, NK cells become frequently dysfunctional in cancer patients, for instance, by downregulation of NK cell activating receptors, disabling them in their antitumor response. In such scenario, ex vivo cultivation can be helpful to arm NK cells with enhanced antitumor properties to overcome immunosuppression. In this review, we summarize the current knowledge on NK cell modulation by different ex vivo cultivation strategies focused on increasing NK cytotoxicity for clinical application in malignant diseases. Moreover, we critically discuss the technical and regulatory aspects and challenges underlying NK cell based therapeutic approaches in the clinics.

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Ex Vivo Activation of CD56+ Immune Cells That Eradicate Neuroblastoma

Cited by 24 publications

References 37 publications

Loss of expression of the Neural Cell Adhesion Molecule 1 (NCAM1) in atypical teratoid/rhabdoid tumors: a new diagnostic marker?

Loss of expression of the Neural Cell Adhesion Molecule 1 (NCAM1) in atypical teratoid/rhabdoid tumors: a new diagnostic marker?

Involvement of IL-10 and TGF-β in HLA-E-mediated neuroblastoma migration and invasion

Shaping of Natural Killer Cell Antitumor Activity by Ex Vivo Cultivation

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