Preferred Label : Autologous CD19CAR-CD28-CD137/CD27/CD3zeta-iCasp9-expressing T-lymphocytes;
NCIt synonyms : 4SCAR19 Cells; Autologous CD19- scFv/CD28/CD137/CD27/CD3z-iCasp9 4SCAR-19 T-cells; 4S-CAR-T19; Autologous Anti-CD19 CAR-T cells 4SCAR19; Autologous CD19-scFv/CD28/CD137/CD27/CD3z-iCasp9 CAR-T-cells;
NCIt definition : Autologous T-lymphocytes that have been transduced with a fourth generation-lentiviral
vector to express the 4SCAR19 gene composed of a chimeric antigen receptor (CAR) consisting
of a single chain variable fragment (scFv) of anti-CD19 coupled to the co-stimulatory
molecules CD28, 4-1BB (CD137), and CD27, and to the cytoplasmic portion of the zeta
chain of the human T-cell receptor (CD3zeta), and containing the apoptosis-inducible
suicide gene human caspase 9 (iCASP9 or iC9), that is linked to a drug binding domain,
with potential immunostimulating and antineoplastic activities. The iCASP9 construct
consists of the entire coding sequence for the human FK506-drug binding protein (FKBP12)
with an F36V mutation (FKBP12-F36V) that is linked to the gene encoding iC9, which
is a modified form of the CASP9 gene where the sequences encoding the endogenous caspase
activation and recruitment domains have been deleted. Upon transfusion, anti-CD19-CAR-CD28/CD137/CD27/CD3zeta-iCasp9-expressing
autologous T-lymphocytes target and bind to CD19-expressing neoplastic B-cells. This
results in a cytotoxic T-lymphocyte (CTL) response against CD19-expressing tumor cells,
and causes tumor cell lysis. If the administered T-cells cause unacceptable side effects,
the chemical homodimerizer AP1903, which binds to the FKBP12-F36V drug-binding domain,
can be administered; this induces caspase 9 expression, and results in apoptosis of
the administered 4SCAR19 T-cells. CD19, cluster of differentiation 19, is a B-cell-specific
cell surface antigen overexpressed in B-cell lineage tumors. Incorporation of the
costimulatory signaling domains increases human T-cell function, expansion, and survival.;
Molecule name : 4SCAR19;
NCI Metathesaurus CUI : CL550792;
Origin ID : C148156;
UMLS CUI : C4724856;
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
