Preferred Label : Autologous NKG2D CAR-CD3zeta-DAP10-expressing T-Lymphocytes CYAD-01;
NCIt synonyms : Autologous CM-CS1 T Cells; Autologous CAR NKG2D; Autologous NKG2D CAR-CD3zeta-DAP10-expressing T-cells CYAD-01; Autologous NKR-2 CAR-T Cells; Autologous NKR 2 T-cells; Autologous CAR-T NKG2D; Autologous CAR-T NKR-2;
NCIt definition : A preparation of autologous peripheral blood T-lymphocytes (PBTLs) that have been
genetically modified and transduced with a retroviral vector to express a chimeric
antigen receptor (CAR) encoding full-length human natural-killer group 2, member D
receptor protein (NKG2D or KLRK1) fused to the CD3zeta cytoplasmic signaling domain
and containing the naturally-expressed adaptor molecule DNAX-activating protein of
10 kDa (DAP10), with potential immunostimulating and antineoplastic activities. Upon
infusion back into the patient, autologous NKG2D CAR-CD3zeta-DAP10-expressing T-lymphocytes
CYAD-01 specifically recognize and bind to tumor cells expressing NKG2D ligands. This
induces secretion of pro-inflammatory cytokines and results in the lysis of NKG2D
ligand-expressing tumor cells. In addition, CYAD-01 targets, binds to and kills NKG2D
ligand expressing tumor-associated endothelial cells in the neovasculature and immunosuppressive
cells, such as regulatory T-cells (Tregs) and myeloid-derived suppressor cells (MDSCs)
in the tumor microenvironment (TME) that express NKG2D ligands. It also activates
macrophages within the TME. Ligands for NKG2D, such as MHC class I chain-related protein
A (MICA), MICB, and members of the UL16-binding proteins (ULBP)/retinoic acid early
transcript 1 (RAET1) family, are overexpressed on infected cells and most cancer cell
types, but are not expressed on most normal, healthy cells. NKG2D, a dimeric, type
II transmembrane protein expressed on human natural killer (NK) and certain T-cells,
in association with the natural adaptive protein DAP10, promotes the elimination of
NKG2D ligand-expressing cells. The CD3zeta signaling domain and DAP10 provide co-stimulatory
signaling upon ligand binding, enhance the secretion of pro-inflammatory cytokines
in response to binding to NKG2D ligand-expressing tumor cells and enhances T-cell
cytotoxicity. DAP10 also associates with and stabilizes NKG2D, which facilitates expression
of the NKG2D-CAR-CD3zeta construct at the cell surface.;
Molecule name : NKR-2; CYAD-101; CM-CS-1; NKR 2; CM CS-1; CYAD-01;
Origin ID : C121536;
UMLS CUI : C4055424;
Semantic type(s)
- Cell [UMLS semantic type]
- chemical_or_drug_affects_cell_type_or_tissue
- chemical_or_drug_has_mechanism_of_action
- chemical_or_drug_has_physiologic_effect
- concept_is_in_subset
- has_target
