NAV

NKG2D-ACE2 CAR-NK Cell

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

Identification

Generic Name
NKG2D-ACE2 CAR-NK Cell
DrugBank Accession Number
DB15727
Background

These cells are prepared as universal off-the-shelf CAR-NK cells from cord blood with NKG2D-ACE2 proteins engineered as part of the CARs; the cell secretes IL-15 and GM-CSF. Chimeric antigen receptors (CARs) are artificial receptors consisting of an antibody-derived antigen binding domain and transmembrane and signaling domains from T-cell receptor signalling moieties. First used with autologous human T cells (CAR-T) as cancer immunotherapies, these receptors are now being engineered onto natural killer (NK) cells due to lower potential for graft-versus-host disease and cytokine release syndrome. The IL-15 superagonist increases the activity of NK cells and improves their target cytotoxicity. The GM-CSF acts as a neutralizer for the CAR-T cell-mediated cytokine release and neurotoxicity. The transmembrane NKG2D and intracellular 2B4 domains are required for optimal NK signalling and subsequent cell-mediated cytotoxicity. The ACE2 is a receptor for SARS-Cov-2, binding to the S-protein of the viral envelope and competitively inhibiting SARS-Cov-2 infection of type II alveolar epithelial cells.

Type
Biotech
Groups
Investigational
Biologic Classification
Cell transplant therapies
Other cell transplant therapies
Synonyms
  • ACE2 CAR-Natural Killer Cell
  • ACE2 CAR-NK Cell
  • NKG2D CAR-Natural Killer Cell
  • NKG2D CAR-NK Cell
  • NKG2D-ACE2 CAR-Natural Killer Cell
External IDs
  • NKG2D-ACE2 CAR-NK Cell
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Pharmacology

Indication

Not Available

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Pharmacodynamics

Not Available

Mechanism of action

NK cells modified by CARs play a role in targeted immunotherapy without subsequent cytokine release syndrome or neurotoxicity as these effects are mediated through GM-CSF neutralization. The NKG2D-ACE2 CAR-NK cells secreting super IL15 superagonist and GM-CSF neutralizing scFv is thought to act synergistically to target and kill cells infected with SARS-Cov-2 without widespread cytokine release and inflammation.

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

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

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.
Not Available
Food Interactions
Not Available

Categories

Drug Categories
Not Available
Classification
Not classified
Affected organisms
Not Available

Chemical Identifiers

UNII
Not Available
CAS number
Not Available

References

General References
  1. 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]
  2. Siegler EL, Zhu Y, Wang P, Yang L: Off-the-Shelf CAR-NK Cells for Cancer Immunotherapy. Cell Stem Cell. 2018 Aug 2;23(2):160-161. doi: 10.1016/j.stem.2018.07.007. [Article]
  3. Li Y, Hermanson DL, Moriarity BS, Kaufman DS: Human iPSC-Derived Natural Killer Cells Engineered with Chimeric Antigen Receptors Enhance Anti-tumor Activity. Cell Stem Cell. 2018 Aug 2;23(2):181-192.e5. doi: 10.1016/j.stem.2018.06.002. Epub 2018 Jun 28. [Article]
  4. TheScientist: Natural Killer Cell Therapies Catch Up to CAR T [Link]
Not Available

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2Unknown StatusTreatmentCoronavirus Disease 2019 (COVID‑19)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 at August 11, 2020 18:53 / Updated at August 13, 2020 07:02