Preferred Label : Autologous FRa-4SCAR-expressing T-cells 4SCAR-FRa;
NCIt synonyms : Autologous 4S-FRa-CAR-T Cells; 4SCAR-FRa; Chimeric Antigen Receptor T Cells 4SCAR-FRa; Autologous Anti-FRa-CD28-CD137-CD27-CD3z-iCasp9 CAR T-cells 4SCAR-FRa; FRa-specific 4th Generation CART Cells;
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-folate receptor alpha (FRa; folate
receptor 1; FOLR1) 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 (CD3zeta;
CD3z), and is fused with the suicide gene inducible caspase 9 (iCasp9), with potential
immunostimulating and antineoplastic activities. Upon administration, autologous FRa-4SCAR-expressing
T-cells 4SCAR-FRa are directed to and induce selective toxicity in FRa-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.
FRa is overexpressed in various tumor cell types, and 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.;
NCI Metathesaurus CUI : CL552500;
Origin ID : C150698;
UMLS CUI : C4725932;
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
