Natural Killer Cell

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Natural Killer Cell
Accession Number
DB15721
Description

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.

Type
Biotech
Groups
Investigational
Biologic Classification
Cell transplant therapies
Other cell transplant therapies
Synonyms
  • NK Cells
External IDs
  • Natural Killer Cells

Pharmacology

Indication
Not Available
Contraindications & Blackbox Warnings
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Pharmacodynamics
Not Available
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.

Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half-life
Not Available
Clearance
Not Available
Adverse Effects
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Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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Not Available
Food Interactions
Not Available

Products

Categories

Drug Categories
Not Available
Classification
Not classified

Chemical Identifiers

UNII
Not Available
CAS number
Not Available

References

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. [PubMed:30325244]
  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. [PubMed:29512837]
  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. [PubMed:31411057]
  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. [PubMed:23906377]
  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. [PubMed:32334062]
  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. [PubMed:28823521]
  7. TheScientist: Natural Killer Cell Therapies Catch Up to CAR T [Link]
Wikipedia
Natural_killer_cell

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2Active Not RecruitingTreatmentEwing's Sarcoma (ES) / Neuroblastomas / Rhabdomyosarcomas / Sarcoma, Osteogenic / Tumors of the Central Nervous System1
2Active Not RecruitingTreatmentNeuroblastomas1
2Active Not RecruitingTreatmentRecurrent B-Cell Childhood Acute Lymphoblastic Leukemia / Recurrent Childhood B-Lymphoblastic Lymphoma1
2CompletedTreatmentAcute Myeloid Leukemia (AML) / Myelodysplastic Syndrome1
2CompletedTreatmentBreast Cancer / Fallopian Tube Cancer / Ovarian Cancer / Primary Peritoneal Cancer1
2CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Non-Hodgkin's Lymphoma (NHL)1
2CompletedTreatmentExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Nodal marginal zone B-cell lymphomas / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Diffuse Mixed Cell Lymphoma / Recurrent Adult Diffuse Small Cleaved Cell Lymphoma / Recurrent Adult Hodgkin's Lymphoma / Recurrent Adult Immunoblastic Large Cell Lymphoma / Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Mycosis Fungoides/Sezary Syndrome / Recurrent Small Lymphocytic Lymphoma / Splenic Marginal Zone Lymphoma / Waldenström's Macroglobulinemia (WM)1
2CompletedTreatmentExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Nodal marginal zone B-cell lymphomas / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Small Lymphocytic Lymphoma / Splenic Marginal Zone Lymphoma1
2CompletedTreatmentHepatocellular Carcinoma1
2CompletedTreatmentLeukemias / Myelodysplastic Syndromes (MDS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available

Drug created on August 11, 2020 11:46 / Updated on August 13, 2020 01:02

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