A simple method for in vitro preparation of natural killer cells from cord blood

Mu, Yong Xu; Zhao, Yu; Li, Bing Yao; Bao, Hong; Jiang, Hui; Qi, Xiao; Bai, Li Yun; Wang, Yun Hong; Jie, Zhi; Wu, Xiao Yun

doi:10.1186/s12896-019-0564-0

Cited by 20 publications

(19 citation statements)

References 29 publications

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“…Typically, a dose of UCB or placenta donor can be expended to an amount sufficient for one adoptive transfer procedure. For instance, 21-day NK culture of placenta-isolated NKs yields an average of 1.2 × 10 9 NK cells with around 80% viability [ 106 ] and 1.59 × 10 10 NK cells with an average purity of 92.37% from UCB [ 107 ].…”

Section: Main Textmentioning

confidence: 99%

“…A more simplified NK cell expansion method has been used by combining group A streptococcus and zoledronate with IL-2 to stimulate UCB-derived mononuclear cells. This method resulted in a 1,560-fold expansion of NK cells with a purity of 92.37% after 21 days of ex vivo culture [ 107 ]. This method was advantageous in that it did not require magnetic cell sorting, feeder cells, or multiple cytokines, potentially lowering the cost of production.…”

Section: Main Textmentioning

confidence: 99%

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NK cell-based cancer immunotherapy: from basic biology to clinical development

et al. 2021

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Natural killer (NK) cell is a specialized immune effector cell type that plays a critical role in immune activation against abnormal cells. Different from events required for T cell activation, NK cell activation is governed by the interaction of NK receptors with target cells, independent of antigen processing and presentation. Due to relatively unsophisticated cues for activation, NK cell has gained significant attention in the field of cancer immunotherapy. Many efforts are emerging for developing and engineering NK cell-based cancer immunotherapy. In this review, we provide our current understandings of NK cell biology, ongoing pre-clinical and clinical development of NK cell-based therapies and discuss the progress, challenges, and future perspectives.

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Section: Main Textmentioning

confidence: 99%

Section: Main Textmentioning

confidence: 99%

NK cell-based cancer immunotherapy: from basic biology to clinical development

et al. 2021

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“…IL-15 outperformed IL-2 in this setting for NK cell purity, and a GMP-compliant process is being evaluated in a phase 1 trial treating refractory lymphoma and myeloma in combination with monoclonal antibody therapy, delivering up to 2 £ 10 8 cells/kg [70]. A recent report describes the use of IL-2, zoledronate (a Food and Drug Administration-approved bisphosphonate medication used in the treatment of osteoporosis and bony metastases) and a group A streptococcus preparation as an activating cocktail, resulting in NK expansion from UCB to numbers suitable for clinical use [71]. Zoledronate and group A streptococcus displayed synergistic benefits with regard to the degree and purity (>90%) of NK cell expansion.…”

Section: Feeder-free Nk Cell Expansionmentioning

confidence: 99%

Generating natural killer cells for adoptive transfer: expanding horizons

2021

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Natural killer (NK) cells are unique innate lymphoid cells that have therapeutic potential in adoptive cell transfer-based cancer immunotherapy that has been established across a range of early-phase clinical trials. NK cells for use in adoptive transfer therapies are obtained from various sources, including primary NK cells from peripheral blood or apheresis products (autologous or allogeneic) and umbilical cord blood. NK cells have also been generated from CD34+ hematopoietic progenitors, induced pluripotent stem cells, embryonic stem cells and malignant cell lines. Apheresis-derived NK cell products are often administered after brief cytokine-based ex vivo activation, ideally aiming for in vivo expansion and proliferation. NK cells from other sources or from smaller volumes of blood require a longer period of expansion prior to therapeutic use. Although ex vivo NK cell expansion introduces a concern for senescence and exhaustion, there is also an opportunity to achieve higher NK cell doses, modulate NK cell activation characteristics and apply genetic engineering approaches, ultimately generating potent effector cells from small volumes of readily available starting materials. Herein the authors review the field of clinical-grade NK cell expansion, explore the desirable features of an idealized NK cell expansion approach and focus on techniques used in recently published clinical trials.

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“…To date, various protocols have been employed for ex vivo expansion and differentiation of NK cells from HSC sources; however, there are still several technical hindrances despite using different combinations of cytokines with or without feeder cell lines, and the use of animal and human sera could lead to many It has been shown that the expanded CD34 + cells could be differentiated into a NK cell product with an average purity of 40-60% after 5-7 weeks of culture (Kao et al, 2007;Mu et al, 2019;Spanholtz et al, 2011). Many studies have reached a calculated mean expansion rate of 300-fold during the NK cell generation phase (Spanholtz et al, 2011;Spanholtz et al, 2010).…”

Section: -B-c and 3-a)mentioning

confidence: 99%

Overcoming the UCB HSCs –Derived NK Cells Dysfunctionality through Harnessing RAS/MAPK, IGF-1R and TGF-β Signaling Pathways

Shokouhifar

Sarab

Yazdanifar

et al. 2020

Preprint

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BackgroundNatural killer (NK) cells differentiated from umbilical cord blood (UCB) hematopoietic stem cells (HSCs) may be more suitable for cell-based immunotherapy compared to NK cells from adult donors. This is due to opportunity to choose alloreactive donors and potentially more robust in vivo expansion. However, the cytotoxicity of UCB-HSC derived NK cells against cancer cells might be suboptimal. To overcome this obstacle, we attempted to generate NK cells with potent antitumor activity by targeting RAS/MAPK, IGF-1R and TGF-β signaling pathways.MethodsThe CD34+ cells isolated from human UCB mononuclear cells through MACS with purity of (≥90%) were used to be differentiated into NK cells. After 21 days of induction with SFTG36, IS721 and IL-15/Hsp70 media, NK cells phenotype was studied and their cytotoxicity against K562 human erythroleukemia cell and SKOV3 ovarian carcinoma cells was analyzed.ResultsThe induced NK cells treated with SFTG36/I721 and SFTG36/IS721 growth factor cocktail expressed a phenotype with CD56+16+CD3- and NKG2D+ with mean fluorescence intensity (MFI) of 92.7%±1.45-168.00±19.20 and 93.23%±0.75-168.66±20.00 respectively. These NK cells once activated by IL-15, demonstrated a higher cytotoxicity against K562 (≥90%) (P ≤ 0.001) and SKOV3 tumor cells (≥65%) (P ≤ 0.001) compared to IL-15/Hsp70 activated NK cells.Conclusion The differentiation of ex vivo-expanded CD34+ cells through manipulation of RAS/MAPK, IGF-1R and TGF-β signaling pathways is an efficient approach for generating functional NK cells that can be used for cancer immunotherapy.

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A simple method for in vitro preparation of natural killer cells from cord blood

Cited by 20 publications

References 29 publications

NK cell-based cancer immunotherapy: from basic biology to clinical development

NK cell-based cancer immunotherapy: from basic biology to clinical development

Generating natural killer cells for adoptive transfer: expanding horizons

Overcoming the UCB HSCs –Derived NK Cells Dysfunctionality through Harnessing RAS/MAPK, IGF-1R and TGF-β Signaling Pathways

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