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drug_type
RELEVANT_DRUG
intervention_type
Cellular therapy (autologous CAR T cells)
drug_description
Autologous, gene-edited CD19-directed CAR T-cell therapy with a CD28 costimulatory domain and a 1XX ITAM-modulated CD3ΞΆ chain; the CAR is inserted into the TRAC locus to knock out the endogenous TCR, standardize CAR expression, and reduce tonic signaling/GvHD risk; designed to eliminate CD19+ malignant B cells and enhance persistence while limiting exhaustion.
nci_thesaurus_concept_id
C200264
nci_thesaurus_preferred_term
TRAC Locus Integrated Anti-CD19 19(T2)28z1xx CAR-T Cells
nci_thesaurus_definition
A preparation of T-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) targeting the tumor-associated antigen (TAA) CD19, linked to the co-stimulatory intracellular signaling domains of CD28 and the zeta chain of the TCR/CD3 complex (CD3-zeta) (CD28zeta; CD28z), and inserted into the T-cell receptor alpha constant (TRAC) locus, with potential immunostimulating and antineoplastic activities. Upon administration, the TRAC locus integrated anti-CD19 19(T2)28z1xx CAR-T cells specifically recognize and bind to CD19-expressing tumor cells, resulting in specific T-cell-mediated tumor cell lysis. CD19 antigen is a B-cell specific cell surface antigen overexpressed in B-cell lineage malignancies. CD28 and CD3zeta provide co-stimulatory activity and may enhance the cytotoxic effect and anti-tumor activity of the CAR T-cells. The 19(T2)28z1xx CAR includes a 1928zeta mutant, 1xx, which contains one instead of all three immunoreceptor tyrosine-based activation motifs (iTAMs). This may help prevent counterproductive T-cell differentiation and exhaustion. Integrating the anti-CD19 CAR to the TRAC locus may enhance both T-cell potency and the re-expression of the CAR following exposure to antigen.
drug_mesh_term
Chimeric Antigen Receptor T-Cell Therapy
drug_category
CAR T
drug_class
Cellular Therapy
drug_delivery_route
Intravenous
drug_mechanism_of_action
Autologous T cells are gene-edited to insert a CD19-targeted CAR with CD28 costimulation and a 1XX-modified CD3zeta activation domain into the TRAC locus, knocking out the endogenous TCR. Upon infusion, the cells bind CD19 on B cells, trigger CAR-mediated activation and cytotoxicity, and eliminate malignant B cells. TRAC integration reduces tonic signaling and GvHD risk and standardizes CAR expression, while the 1XX ITAM design tempers signaling to limit exhaustion and improve persistence.
drug_name
19(T2)28z1xx TRAC T cell
nct_id_drug_ref
NCT05757700