Preferred Label : Autologous CD123-4SCAR-expressing T-cells 4SCAR123;
NCIt synonyms : CD123-4SCAR-expressing T Lymphocytes; 4S-CD123-CAR-T Cell; 4SCAR123 T-cells; CD123-scFv/CD28/CD137/CD27/CD3z-iCasp9 T-cells; CD123-specific 4th Generation Chimeric Antigen Receptor-modified T Cells; Anti-CD123-CD28-CD137-CD27-CD3z-iCasp9 CAR T-cells 4SCAR123; Anti-CD123 CAR-T Cells 4SCAR123;
NCIt definition : A preparation of genetically modified autologous T-cells transduced with a replication
incompetent, self-inactivating lentiviral vector expressing a fourth generation chimeric
antigen receptor (4SCAR) consisting of an anti-CD123 (interleukin-3 receptor alpha
chain or IL3RA) single chain variable fragment (scFv) that is coupled to the costimulatory
signaling domains CD28, CD137, CD27 and the zeta chain of the T-cell receptor (TCR),
and is fused with the suicide gene inducible caspase 9 (iCasp9), with potential immunostimulating
and antineoplastic activities. Upon administration, autologous CD123-4SCAR-expressing
T-cells 4SCAR123 are directed to and induce selective toxicity in CD123-expressing
tumor cells. iCasp9 consists of a human FK506 drug-binding domain with an F36V mutation
(FKBP12-F36V) linked to human caspase 9. If the administered T-cells lead to unacceptable
side effects, the chemical homodimerizer AP1903 can be administered. AP1903 binds
to the drug binding FKBP12-F36V domain and induces activation of caspase 9, which
results in the apoptosis of the administered T-cells and enhances safety of this agent.
CD123 is normally expressed on committed blood progenitor cells in the bone marrow;
its overexpression is associated with increased leukemic cell proliferation and aggressiveness.
CD28, CD137 and CD27, T-cell surface-associated co-stimulatory molecules, are required
for full T-cell activation and enhance both proliferation of T-cells and antitumor
activity.;
Molecule name : 4SCAR123;
NCI Metathesaurus CUI : CL551139;
Origin ID : C148526;
UMLS CUI : C4725102;
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
