drug_type
RELEVANT_DRUG
intervention_type
Cellular immunotherapy
drug_description
Autologous gene-modified T cells engineered to express a synthetic antigen receptor targeting LILRB4 (ILT3/CD85k), signaling via the native TCR/CD3 complex to kill LILRB4-positive monocytic leukemia cells.
nci_thesaurus_concept_id
C192644
nci_thesaurus_definition
A preparation of autologous T-lymphocytes that have been genetically modified and transduced with a lentiviral vector expressing a T-cell-receptor (TCR) complex-based chimeric antigen receptor (CAR) specific for two different epitopes of the immune inhibitory receptor leukocyte immunoglobulin-like receptor B member 4 (LILRB4; ILT3; ILT-3), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, autologous anti-LILRB4 CAR-T cells target and bind to two different epitopes of LILRB4 expressed on tumor cells. This results in a cytotoxic T-lymphocyte (CTL) response against LILRB4-expressing tumor cells. LILRB4, a tumor associated antigen (TAA) and an immune inhibitory receptor expressed on immune suppressive myeloid cells, is highly expressed on certain hematologic cancer cells, such as monocytic acute myeloid leukemia (AML) cells. It functions as an immune checkpoint that negatively regulates T-cell activation as its extracellular domain inhibits T-cell activity. It plays an important role in tumor infiltration, T-cell suppression and immune tolerance.
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 are genetically engineered to express a STAR receptor that targets LILRB4 (ILT3/CD85k). The STAR assembles with the native TCR/CD3 complex, so antigen binding on LILRB4-positive monocytic leukemia cells triggers TCR/CD3 signaling, activating the T cells to proliferate and kill targets via perforin/granzyme-mediated cytotoxicity, thereby eliminating LILRB4-expressing leukemia and immunosuppressive myeloid cells.
drug_name
LILRB4 STAR-T cells
nct_id_drug_ref
NCT05739409