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drug_type
RELEVANT_DRUG
intervention_type
Cellular therapy (CAR T)
drug_description
Autologous GPC3-targeted chimeric antigen receptor T-cell (CAR-T) therapy for advanced/recurrent hepatocellular carcinoma; patient T cells are collected via leukapheresis, engineered ex vivo to express a GPC3-specific CAR, and reinfused to mediate antigen-directed cytotoxicity.
nci_thesaurus_concept_id
C202234
nci_thesaurus_preferred_term
Autologous dnTGF-BRII-armored Anti-GPC3 CAR T-cells AZD5851
nci_thesaurus_definition
A preparation of autologous T-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) specific for glypican-3 (GPC3) 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-GPC3 CAR T-cells AZD5851 are directed to and induce selective toxicity in GPC3-expressing tumor cells. GPC3, a heparan sulfate proteoglycan and a member of the glypican family, is overexpressed on certain tumor cell types while minimally expressed on normal, healthy cells; GPC3 plays an important role in cellular proliferation and differentiation. The inclusion of dnTGF-BRII blocks the signaling of the immunosuppressive cytokine TGFb in the tumor microenvironment (TME) and makes the AZD5851 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 Therapy
drug_category
CAR T
drug_class
Cellular Therapy
drug_delivery_route
Intravenous
drug_mechanism_of_action
Autologous T cells engineered with a GPC3-specific chimeric antigen receptor recognize glypican-3 on tumor cells, triggering T-cell activation, proliferation, cytokine release, and perforin/granzyme-mediated cytotoxicity against GPC3-positive cells. The cells are armored with a dominant-negative TGF-beta receptor II to block TGF-beta signaling in the tumor microenvironment, increasing resistance to immunosuppression and enhancing antitumor activity.
drug_name
AZD5851
nct_id_drug_ref
NCT06084884