drug_type
RELEVANT_DRUG
intervention_type
Cellular therapy (autologous genetically engineered CAR T cells)
drug_description
An autologous, genetically engineered Tmod CAR T-cell therapy with a dual-receptor logic gate: an activator CAR targets carcinoembryonic antigen (CEA) and a blocker receptor recognizes HLA-A*02 on normal cells. The cells activate only in CEA-positive tumor cells lacking HLA-A*02 (AND-NOT gating) to spare normal CEA-expressing tissues. Investigated post-lymphodepletion for CEA+ solid tumors with HLA-A*02 loss of heterozygosity.
nci_thesaurus_concept_id
C199653
nci_thesaurus_preferred_term
Autologous Anti-CEA CAR/HLA-A*02-gated Inhibitory Receptor/B2M shRNA-expressing T-lymphocytes A2B530
nci_thesaurus_definition
A preparation of autologous T-lymphocytes from a human leukocyte antigen (HLA)-A*02-positive donor that have been transduced with a lentiviral vector expressing an activating chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) carcinoembryonic antigen-related cell adhesion molecule 5 (CEA or CEACAM5), a leukocyte immunoglobulin-like receptor 1 (LIR-1)-based inhibitory receptor specific for HLA-A*02, and a short hairpin RNA (shRNA) targeting beta-2 microglobulin (B2M), with potential immunomodulating and antineoplastic activities. Upon administration, the autologous anti-CEA CAR/HLA-A*02-gated inhibitory receptor/B2M shRNA-expressing T-lymphocytes A2B530 target and bind to CEA-expressing tumor cells, thereby killing CEA-expressing tumor cells. The inhibitory receptor specific for HLA-A*02 acts as a safety switch that blocks the killing of HLA-A*02-positive CEA-expressing normal cells. HLA-A*02 is expressed on normal cells but not on tumor cells due to loss of heterozygosity (LOH). The B2M shRNA disrupts the expression of the B2M component of the HLA class I molecule. CEA, a member of the CEA family of proteins, plays a key role in cell migration, cell invasion and cell adhesion, and is overexpressed by a variety of cancer types.
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 dual-receptor logic gate: an activating CAR targets CEA to trigger cytotoxicity, while an HLA-A*02–specific inhibitory receptor (LIR-1–based) blocks activation on HLA-A*02–positive normal cells. This AND-NOT gating enables killing only of CEA-positive tumor cells that have lost HLA-A*02. An shRNA against B2M reduces HLA class I expression on the engineered T cells.
drug_name
A2B530
nct_id_drug_ref
NCT05736731