drug_type
RELEVANT_DRUG
intervention_type
Cellular therapy (autologous CAR T cells)
drug_description
Autologous, lentivirally transduced second-generation CAR T-cell therapy (CD4+ and CD8+) targeting B7-H3 (CD276), EGFR806 epitope on EGFR/EGFRvIII, HER2 (ERBB2), and IL13Rα2 via an IL13-zetakine design; administered locoregionally via intraventricular catheter to drive CAR-mediated cytotoxic killing of CNS tumor cells and mitigate antigen escape.
nci_thesaurus_concept_id
C200272
nci_thesaurus_definition
A preparation of autologous CD4+ and CD8+ T-lymphocytes transduced with a lentiviral vector to express four chimeric antigen receptors (CARs) targeting the immunoregulatory protein B7-homologue 3 (B7-H3, CD276), epidermal growth factor receptor (EGFR) mAb806 epitope, human epidermal growth factor 2 (HER2; ErbB2; HER-2), and interleukin-13 receptor alpha 2 (IL13Ra2), with potential immunostimulating and antineoplastic activities. Upon administration, autologous B7-H3/EGFR806/HER2/IL13-zetakine CAR-expressing CD4+/CD8+ T-cells SC-CAR4BRAIN target and bind to tumor cells that express B7-H3, EGFR mAb806 epitope, HER2 and IL13Ra2, thereby inducing selective toxicity in these cells. B7-H3, a type I transmembrane protein and a member of the B7 co-stimulatory protein superfamily, is overexpressed on certain tumor cell types and on various immune cells. It is a negative regulator of T-cell activation and its overexpression plays a key role in tumor cell invasion and metastasis. EGFR, overexpressed by a variety of cancer cell types, plays a key role in tumor cell proliferation, tumor angiogenesis and radio- and chemoresistance. EGFR806 CAR specifically targets abnormal conformational states of EGFR, including EGFR deletion mutation variant III (EGFRvIII), and activating mutations, with lower affinity for wild-type EGFR. HER2 is overexpressed in a variety of cancer cell types and is associated with increased tumor cell proliferation. IL13Ra2, a cancer-associated receptor, is overexpressed by a variety of tumor cell types including glioblastoma multiforme (GBM); it is associated with increased invasiveness of tumor cells.
drug_mesh_term
Chimeric Antigen Receptor T-Cell Therapy
drug_category
CAR T
drug_class
Cellular Therapy
drug_delivery_route
Intracerebroventricular
drug_mechanism_of_action
Autologous CD4+/CD8+ T cells are lentivirally engineered to express four second-generation CARs targeting B7-H3 (CD276), the tumor-restricted EGFR806 epitope on EGFR/EGFRvIII, HER2, and IL13Ra2 (via an IL13-zetakine design). Following locoregional intraventricular delivery, CAR engagement drives antigen-specific T-cell activation, cytokine release, and cytotoxic killing of CNS tumor cells, with multi-antigen targeting intended to mitigate antigen escape.
drug_name
SC-CAR4BRAIN
nct_id_drug_ref
NCT05768880