drug_type
RELEVANT_DRUG
intervention_type
Cellular therapy (CAR T cells)
drug_description
Autologous, gene-modified CD19-directed CAR T-cell therapy co-expressing an engineered orthogonal IL-2 receptor beta (hoRb); eliminates CD19+ B cells and can be selectively expanded/activated via hoRb signaling.
nci_thesaurus_concept_id
C192137
nci_thesaurus_preferred_term
Autologous CD19 CAR-expressing T-cells YTB323
nci_thesaurus_definition
A preparation of autologous T-lymphocytes that have been genetically modified and transduced with a lentiviral vector expressing a chimeric antigen receptor (CAR) targeting the tumor-associated antigen (TAA) CD19 fused to the extracellular, transmembrane and intracellular signaling domains of the T-cell co-stimulatory receptor CD28 and the cytoplasmic signaling domain of the zeta chain of the TCR/CD3 complex (CD3-zeta) and expressing a mutated orthogonal (ortho) interleukin (IL)-2beta receptor (hoRbeta; hoRb), with potential immunostimulating and antineoplastic activities. Upon administration, autologous hoRb-expressing anti-CD19 CAR T-cells SYNCAR-001 target and bind to CD19-expressing tumor cells, thereby inducing selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. Stimulation of hoRb specifically by orthogonal (ortho) IL-2 STK-009 allows for IL-2 signaling specifically in SYNCAR-001 and leads to increased proliferation, persistence and anti-tumor activity of SYNCAR-001. This may lead to dose reduction of SYNCAR-001. hoRb does not respond to the native IL-2 ligand. As STK-009 does not cause IL-2-mediated signaling in other immune cells, systemic toxicity is limited.
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 engineered with a CD19-directed CAR (CD28 costimulation + CD3ζ signaling) to recognize and kill CD19+ B cells via T-cell activation and cytolytic pathways. The cells co-express an engineered orthogonal IL-2 receptor β (hoRb), enabling selective expansion and activation upon administration of the matching orthogonal IL-2 (e.g., STK-009), which signals through JAK/STAT in the modified T cells only, enhancing proliferation, persistence, and antitumor activity while limiting systemic IL-2–mediated effects.
drug_name
SYNCAR-001
nct_id_drug_ref
NCT05665062