drug_type
RELEVANT_DRUG
intervention_type
Cellular therapy (autologous CAR T cells)
drug_description
Autologous CAR T-cell therapy engineered to express a STEAP2-specific chimeric antigen receptor; upon binding STEAP2 on prostate cancer cells, it activates T cells to proliferate, release cytokines, and lyse STEAP2-positive tumor cells. Administered intravenously after lymphodepleting chemotherapy.
nci_thesaurus_concept_id
C204477
nci_thesaurus_preferred_term
Autologous dnTGF-BRII-armored Anti-STEAP2 CAR T-cells AZD0754
nci_thesaurus_definition
A preparation of autologous T-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) specific for the metalloreductase six-transmembrane epithelial antigen of prostate-2 (STEAP2; STAMP1) and the dominant negative (dn) form of transforming growth factor-beta (TGF-beta; TGFb) receptor 2 (dnTGF-BRII; dnTGFbR2), with potential immunomodulating and antineoplastic activities. Upon reintroduction into the patient, autologous dnTGF-BRII-armored anti-STEAP2 CAR T-cells AZD0754 are directed to and induce selective toxicity in STEAP2-expressing tumor cells. STEAP2 is a cell surface antigen overexpressed in prostate cancer with limited expression in normal tissue. The inclusion of dnTGF-BRII blocks the signaling of the immunosuppressive cytokine TGFb in the tumor microenvironment (TME) and makes the AZD0754 CAR T-cells resistant to TGFb. TGFb negatively regulates T-cell proliferation and activation and plays a key role in tumor immune suppression.
drug_mesh_term
Chimeric Antigen Receptor T-Cell Immunotherapy
drug_category
CAR T
drug_class
Cellular Therapy
drug_delivery_route
Intravenous
drug_mechanism_of_action
Autologous T cells engineered to express a STEAP2-specific CAR and a dominant-negative TGF-β receptor II. Upon binding STEAP2 on prostate cancer cells, CAR signaling activates T cells to proliferate, secrete cytokines, and kill target cells via cytotoxic mechanisms, while the dnTGFBRII blocks immunosuppressive TGF-β signaling to enhance activity in the tumor microenvironment.
drug_name
AZD0754
nct_id_drug_ref
NCT06267729