Synergistic cytotoxicity of ex vivo expanded natural killer cells in combination with monoclonal antibody drugs against cancer cells

Deng, Xuewen; Nieda, Mie; Xiao, Weihua; Nicol, Andrew

doi:10.1016/j.intimp.2012.09.014

Cited by 39 publications

(29 citation statements)

References 57 publications

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“…NK cells that have been ex vivo expanded using these modified K562 cells have better anti-tumor activity in vitro and in vivo in mouse models ( 166 ). In addition, ex vivo -expanded NK cells have also been shown to be able to mediate ADCC, and in combination with tumor antigen-specific antibodies, they exerted better anti-tumor efficacy ( 167 , 168 ). Different protocols using expanded NK cells are currently under clinical testing, either alone or in combination with tumor-specific mAb ( 169 – 171 ).…”

Section: How To Augment Anti-tumor Effects Of Adccmentioning

confidence: 99%

NK cell-mediated antibody-dependent cellular cytotoxicity in cancer immunotherapy

et al. 2015

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Natural killer (NK) cells play a major role in cancer immunotherapies that involve tumor-antigen targeting by monoclonal antibodies (mAbs). NK cells express a variety of activating and inhibitory receptors that serve to regulate the function and activity of the cells. In the context of targeting cells, NK cells can be “specifically activated” through certain Fc receptors that are expressed on their cell surface. NK cells can express FcγRIIIA and/or FcγRIIC, which can bind to the Fc portion of immunoglobulins, transmitting activating signals within NK cells. Once activated through Fc receptors by antibodies bound to target cells, NK cells are able to lyse target cells without priming, and secrete cytokines like interferon gamma to recruit adaptive immune cells. This antibody-dependent cell-mediated cytotoxicity (ADCC) of tumor cells is utilized in the treatment of various cancers overexpressing unique antigens, such as neuroblastoma, breast cancer, B cell lymphoma, and others. NK cells also express a family of receptors called killer immunoglobulin-like receptors (KIRs), which regulate the function and response of NK cells toward target cells through their interaction with their cognate ligands that are expressed on tumor cells. Genetic polymorphisms in KIR and KIR-ligands, as well as FcγRs may influence NK cell responsiveness in conjunction with mAb immunotherapies. This review focuses on current therapeutic mAbs, different strategies to augment the anti-tumor efficacy of ADCC, and genotypic factors that may influence patient responses to antibody-dependent immunotherapies.

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Section: How To Augment Anti-tumor Effects Of Adccmentioning

confidence: 99%

NK cell-mediated antibody-dependent cellular cytotoxicity in cancer immunotherapy

et al. 2015

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“…The Fc receptor CD16 is crucial for NK cells to perform ADCC and would be of particular importance for potential combination therapies using NK cells together with therapeutic antibodies. Of note, although reduced levels of CD16 on NK cells are observed for several NK cell cultivation protocols the NK cells still mediate ADCC (70, 129, 142). Nevertheless, inhibition of the relevant metalloproteases to maintain CD16 on NK cells could be an option to further increase the ADCC function of ex vivo activated NK cells (164, 167).…”

Section: Discussionmentioning

confidence: 99%

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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“…The procedure for the expansion of activated immune cells using an expansion kit (BINKIT ® , BIJ, Japan) is described below [5], [6]. A description of the quality tests used to analyze surface markers is omitted in this report.…”

Section: Methodsmentioning

confidence: 99%

Experience of contamination during autologous cell manufacturing in cell processing facility under the Japanese Medical Practitioners Act and the Medical Care Act

Mizutani

Samejima

Kino‐oka

2016

Regenerative Therapy

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Cell therapy and regenerative medicine technologies require strict cell manufacturing procedures to be defined and addressed. Maintenance of the aseptic environment is critical to preclude extrinsic contamination risks, similar to conventional pharmaceutical manufacturing. However, intrinsic contamination risks exist in all cell manufacturing processes owing to the use of cells as the raw materials that cannot be sterilized, thus giving rise to the primary and secondary risks of cell contamination and cross-contamination, respectively. Analysis of contamination risks was conducted on experienced batches (29,858 batches) for the production of immune cells derived from autologous blood mononuclear cells under the Medical Practitioners Act and the Medical Care Act in Japan. From these batches, 0.06% (18 cases) of contamination occurred, representing low probability of contamination incidence during cell processing. Almost all the causes of these contaminations were regarded to be from the collected blood (intrinsic contamination), and subsequent cross-contaminations were prevented, considering that the secondary contamination risk can be reduced by adequate managements of operational procedures for changeover in aseptic environment.

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Synergistic cytotoxicity of ex vivo expanded natural killer cells in combination with monoclonal antibody drugs against cancer cells

Cited by 39 publications

References 57 publications

NK cell-mediated antibody-dependent cellular cytotoxicity in cancer immunotherapy

NK cell-mediated antibody-dependent cellular cytotoxicity in cancer immunotherapy

Shaping of Natural Killer Cell Antitumor Activity by Ex Vivo Cultivation

Experience of contamination during autologous cell manufacturing in cell processing facility under the Japanese Medical Practitioners Act and the Medical Care Act

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