drug_type
RELEVANT_DRUG
intervention_type
Biological (tetra-specific antibody)
drug_description
An intravenously administered tetra-specific antibody (biologic immunotherapy) engineered to engage CD3 on T cells and recognize multiple B-cell-associated antigens to redirect and activate T cells against B-cell lymphoma, aiming to enhance cytotoxicity, provide costimulation/checkpoint modulation, and reduce antigen escape.
nci_thesaurus_concept_id
C178448
nci_thesaurus_definition
An anti-CD19/anti-CD3/anti-PD-L1/anti-4-1BB tetra-specific antibody, with potential immunostimulatory and antineoplastic activities. Upon administration, emfizatamab targets and binds to the tumor-associated antigen (TAA) CD19 overexpressed on the surface of B-cells, the immunosuppressive ligand programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274) expressed on tumor cells, the T-cell surface antigen CD3 and the costimulatory receptor 4-1BB (CD137; tumor necrosis factor receptor superfamily member 9; TNFRSF9) expressed on a variety of leukocyte subsets including activated T-lymphocytes. This may crosslink CD19-expressing tumor B-cells and cytotoxic T-lymphocytes (CTLs) and result in a potent CTL-mediated cell lysis of CD19-expressing B-lymphocytes. In addition, 4-1BB binding results in T-cell co-stimulation and enhanced anti-tumor activity. At the same time, GNC-038 prevents PD-L1 from binding to and activating its receptor, programmed cell death 1 (PD-1; PDCD1; CD279; programmed death-1). This abrogates T-cell inhibition, activates antigen-specific T-lymphocytes and enhances CTL-mediated tumor cell lysis, which may lead to a reduction in tumor growth. PD-L1 binding to PD-1 on activated T-cells inhibits the expansion and survival of CD8-positive T-cells, suppresses the immune system and results in immune evasion. 4-1BB, a surface glycoprotein of the tumor necrosis factor receptor superfamily, is an inducible costimulatory receptor that plays a key role in T-cell proliferation, survival and cytolytic activity. CD19, a B-cell specific membrane antigen, is expressed during normal B-cell development and on B-cell malignancies.
drug_category
TRISPECIFIC T ENGAGER
drug_class
Engager
drug_delivery_route
Intravenous
drug_mechanism_of_action
Tetra-specific T-cell–redirecting antibody that binds CD3 on T cells, CD19 on B-cell lymphomas, PD-L1 to block PD-1–mediated inhibition, and 4-1BB to provide costimulation. By crosslinking T cells to CD19+ tumor cells, it induces CTL-mediated killing while concurrently enhancing activation and persistence and reducing antigen escape.
drug_name
GNC-038
nct_id_drug_ref
NCT05485753