Natural Killer Cell

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Generic Name
Natural Killer Cell
DrugBank Accession Number

Natural Killer (NK) cells originate and differentiate from hematopoietic stem cells through various signalling pathways involving cytokines and interleukins. These cells arise from CD34+ lymphoid progenitors and comprise 10-15% of all lymphocytes in human peripheral blood. Once completely differentiated, NK cells lack B (CD19-) and T(CD3-) lymphocyte markers and carry their unique CD56+ status instead. The two maturate variants of NK cells are CD56dim and CD56bright, which exert cytotoxicity through release of toxic chemicals and cytokine secretion, respectively. NK Cells express features of innate immune responses, and respond to all molecules that appear to be foreign to the body.

The most standard and utilized source of NK cells is directly from the peripheral blood of a donor through leukapheresis: a technique where immune cells are separated from red blood cells. Generally, the number of NK cells collected in the peripheral blood mononuclear cell (PBMC) is too low for sufficient potency, and ex vivo expansion is performed. Expansion involves the use of feeder cell line systems or bioreactors to enhance the number of NK cells with desired cytotoxicity. These cells are also purified using cell-separation systems and processing.

Other techniques involve using umbilical cord blood (UCB) directly; these NK cells have heterogeneous CD56 expression but are considered suitable for immunotherapy. It is also possible to culture UCB CD34+ hematopoietic stem cells (HSCs) under stimulation of IL-2, IL-15, and stem cell factor (SCF) in a system to develop NK cells.

Induced pluripotent stem cells (iPSCs) and human embryonic stem cells (HESCs) are also used to generate NK cells through a two-step culture method resulting in CD34+ cells.

Biologic Classification
Cell transplant therapies
Other cell transplant therapies
  • NK Cells
External IDs
  • Natural Killer Cells



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Mechanism of action

The predominant targets of NK cells are ‘stressed’ cells with downregulated expression of class I MHC (MHC-I), a common mechanism used by malignant or virus-infected cells to evade recognition by the body’s immune system. In response to encountering these cells, NK cells release two types of proteins, perforins and granzyme B, which attack the target cell’s membrane, damage its organelles, and trigger apoptosis. NK Cell immunotherapy is an emerging anti-cancer strategy, as these cells are able to exert effects without activating the graft-versus-host disease cascade. In addition, their broad mechanism allows for generally safe administration of NK cells that are not immunologically matched to a patient.


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Volume of distribution

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Adverse Effects
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Pharmacogenomic Effects/ADRs
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Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
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Chemical Identifiers

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General References
  1. Suen WC, Lee WY, Leung KT, Pan XH, Li G: Natural Killer Cell-Based Cancer Immunotherapy: A Review on 10 Years Completed Clinical Trials. Cancer Invest. 2018;36(8):431-457. doi: 10.1080/07357907.2018.1515315. Epub 2018 Oct 16. [Article]
  2. Kumar S: Natural killer cell cytotoxicity and its regulation by inhibitory receptors. Immunology. 2018 Jul;154(3):383-393. doi: 10.1111/imm.12921. Epub 2018 Apr 11. [Article]
  3. Choucair K, Duff JR, Cassidy CS, Albrethsen MT, Kelso JD, Lenhard A, Staats H, Patel R, Brunicardi FC, Dworkin L, Nemunaitis J: Natural killer cells: a review of biology, therapeutic potential and challenges in treatment of solid tumors. Future Oncol. 2019 Sep;15(26):3053-3069. doi: 10.2217/fon-2019-0116. Epub 2019 Aug 14. [Article]
  4. Campbell KS, Hasegawa J: Natural killer cell biology: an update and future directions. J Allergy Clin Immunol. 2013 Sep;132(3):536-544. doi: 10.1016/j.jaci.2013.07.006. Epub 2013 Jul 30. [Article]
  5. Zhang J, Xie B, Hashimoto K: Current status of potential therapeutic candidates for the COVID-19 crisis. Brain Behav Immun. 2020 Jul;87:59-73. doi: 10.1016/j.bbi.2020.04.046. Epub 2020 Apr 22. [Article]
  6. Robinson TO, Schluns KS: The potential and promise of IL-15 in immuno-oncogenic therapies. Immunol Lett. 2017 Oct;190:159-168. doi: 10.1016/j.imlet.2017.08.010. Epub 2017 Aug 16. [Article]
  7. TheScientist: Natural Killer Cell Therapies Catch Up to CAR T [Link]

Clinical Trials

Clinical Trials
2Active Not RecruitingTreatmentCentral Nervous System Neoplasm / Ewing's Sarcoma / Neuroblastoma (NB) / Osteosarcoma / Rhabdomyosarcomas1
2Active Not RecruitingTreatmentMultiple Myeloma (MM) / Plasma Cell Leukemia1
2Active Not RecruitingTreatmentNeuroblastoma (NB)1
2CompletedTreatmentAcute Myeloid Leukemia1
2CompletedTreatmentAcute Myeloid Leukemia / Myelodysplastic Syndrome1


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Experimental Properties
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Drug created at August 11, 2020 17:46 / Updated at August 13, 2020 07:02