“Little ‘Life’ Makes Sense (I)” | A Brief Discussion of NK Cells
Release Date:
2023-08-03 17:41
Introduction to NK Cells
Natural killer (NK) cells are potent effector cells of the innate immune system, serving as the first line of defense against diseases, including malignant tumors, and representing the third major class of lymphocytes alongside T cells and B cells. NK cells originate from hematopoietic stem cells in the bone marrow, account for approximately 15% of all immune cells in the blood, and are predominantly found in peripheral blood, the liver, and the spleen. In humans, the defining characteristic of NK cells is a CD3−CD16+/CD56+ lymphocyte population.
Natural killer (NK) cells predominantly exhibit antitumor cytotoxicity. They secrete large amounts of lytic granules, including perforin, granzymes, and human granulysin, which can induce apoptosis in stressed target cells. NK cells also express various tumor necrosis factors (TNFs), such as FASL and TRAIL, which bind to their respective FAS receptor or TRAIL receptor to trigger apoptosis of target cells. In addition, NK cells produce a range of cytokines (e.g., IFN-γ, TNF-α, IL-10), growth factors (e.g., GM-CSF), and chemokines (e.g., CCL3, CCL4, CCL5, XCL1).
Natural killer (NK) cells initiate immune responses through interactions with dendritic cells, macrophages, and T cells. A dynamic balance between inhibitory and activating receptors on the cell surface ensures the fine-tuned regulation of NK cell effector functions. These inhibitory receptors recognize various forms of MHC class I molecules; consequently, a reduction or loss of MHC class I expression on target cells attenuates inhibitory signaling from NK cells, thereby promoting NK cell activation. The engagement of activating receptors and natural cytotoxicity receptors also contributes to NK cell activation. Moreover, NK cells mediate antibody-dependent cellular cytotoxicity (ADCC), which is a critical mechanism underlying the clinical efficacy of currently popular antibody-based therapeutics.
NK cells from different sources
NK cells can be derived from peripheral blood mononuclear cells (PBMCs), umbilical cord blood (UCB), bone marrow (BM), human embryonic stem cells (hESCs), induced pluripotent stem cells (iPSCs), or cell lines through expansion. The large-scale expansion of highly purified, highly active NK cells is a critical factor for their therapeutic application. Therefore, safe and efficient manufacturing methods are essential for generating large quantities of functional NK cells.
Derived from peripheral blood mononuclear cells
NK cells account for only 5–15% of PBMCs; several protocols are currently available for isolating and selectively expanding primary NK cells from PBMCs. These protocols primarily involve immunomagnetic bead-based sorting—either negative or positive selection—to enrich highly purified NK cells, as well as the use of NK cell activation and expansion reagents to expand NK cells from PBMCs and obtain high-purity NK populations.
Umbilical cord blood or bone marrow
CD34+ hematopoietic stem cells derived from umbilical cord blood or bone marrow represent an excellent source for cell therapy applications. Given the relatively low number of NK cells derived from umbilical cord blood, early studies struggled to achieve sufficient NK cell expansion; consequently, various strategies have been developed to generate NK cells from CD34+ hematopoietic stem cells sourced from bone marrow and umbilical cord blood, employing co-culture systems that incorporate stromal cell lines and combinations of cytokines known to promote NK cell development.
Embryonic stem cells or induced pluripotent stem cells
The generation of NK cells from hESCs or iPS cells centers on optimizing the culture conditions for their production; it has been demonstrated that functional NK cells can be efficiently derived from hESCs by selecting CD34+ populations, which exhibit functional receptors and cytolytic activity.
Immortalized NK cell line
Established NK cell lines include NK-92, YT, NKL, HANK-1, KHYG-1, NK-YS, NKG, and NK101. Among these, NK-92 is the only cell line approved by the FDA for Phase 1 and Phase 2 clinical trials. NK-92 is derived from the peripheral blood of a 50-year-old male patient with rapidly progressing non-Hodgkin lymphoma; it can be readily cultured in vitro and, upon addition of recombinant IL-2, can be expanded on a large scale under GMP-compliant conditions. Furthermore, it can be cryopreserved at low temperatures and maintains excellent cellular viability and functional activity after thawing.
Strategies that address the limited availability of NK cells through expansion, combined with GMP-compliant screening and purification protocols, can facilitate NK-cell–based immunotherapies for a wide range of malignancies. To translate these approaches into clinical-grade NK-cell manufacturing, it is essential to optimize GMP-compliant production conditions and to develop robust cryopreservation methods for establishing an NK-cell biobank, thereby substantially enhancing the therapeutic efficacy of NK cells in clinical settings.
Hycells Biotechnology provides NK cell samples, services, and culture media.
1. Purified NK cells derived from PBMCs
Purified NK cells were obtained by immunomagnetic bead sorting.
*Hycells Biotechnology solemnly commits that all cell-service samples provided by our company are fully traceable and compliant with drug-registration requirements.
2. ADCC Assay Services
Effector cell: PBMC or NK cells
Target cell: SK-BR-3
Antibody: Herceptin
Detection: LDH
Assay principle: Lactate dehydrogenase is abundantly present in the cytoplasm. Under normal conditions, it cannot cross the cell membrane; however, upon cell injury or death, it is released into the extracellular space. Therefore, the number of dead cells is directly proportional to the LDH activity in the cell culture supernatant. The LDH activity in the experimental wells is determined by a colorimetric assay and compared with that in the target-cell control wells, allowing calculation of the percentage of target-cell lysis mediated by the effector cells.
ADCC-optimized PBMC
ADCC assays were performed on PBMCs from different donors under identical assay conditions to identify batches with superior ADCC activity.
For additional batches of optimized PBMC in vitro screening data, please contact our sales representative.
Contact: Mr. Xie 15201775322。
3. NK Expansion Culture Medium
During ex vivo expansion and culture of NK cells, challenges often arise, including low expansion rates, prolonged culture durations, and the initial overgrowth of conventional T cells, which can lead to phenotypic exhaustion of the NK cell population. Hycells’s NK cell expansion medium supports rapid, feeder-free expansion of NK cells derived from diverse sources, making it an optimal choice for clinical trials and research in cell therapy. It is broadly applicable for the expansion of NK cells derived from peripheral blood, umbilical cord blood, the NK cell line NK92, and NK cells induced from pluripotent stem cells.
HiXpan TM NK Amplification Kit Set (1L/2L/4L)
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HiXpanTM NK Cell Expansion Medium Serum-Free Culture Medi
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