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drug_type
RELEVANT_DRUG
intervention_type
Biologic - bispecific monoclonal antibody
drug_description
Recombinant humanized bispecific IgG antibody that binds EGFR on tumor cells and agonizes 4-1BB (CD137) on activated T cells/NK cells to provide costimulatory signaling and enhance antitumor immunity.
nci_thesaurus_concept_id
C187697
nci_thesaurus_definition
A recombinant human bispecific antibody targeting both the tumor-associated antigen (TAA) epidermal growth factor receptor (EGFR) and the costimulatory receptor 4-1BB (CD137; tumor necrosis factor receptor superfamily member 9; TNFRSF9), with potential checkpoint inhibitory, immunostimulating and antineoplastic activities. Upon administration, anti-EGFR/anti-4-1BB bispecific antibody HLX35 simultaneously targets and binds to the extracellular domain of EGFR, which is expressed on a variety of tumor cells and 4-1BB, which is expressed on activated T-lymphocytes, natural killer (NK) cells and NK-T-cells. This crosslinks EGFR-expressing tumor cells and 4-1BB-expressing T-cells. The binding to EGFR inactivates EGFR and prevents EGFR-mediated signaling. Through 4-1BB binding, HLX35 acts as a conditional 4-1BB agonist, resulting in cytotoxic T-cell co-stimulation and enhances T-lymphocyte-mediated anti-tumor activity. It also activates memory T-cells, NK cells and dendritic cells (DCs) in the tumor microenvironment (TME). This activates antigen-specific T-lymphocytes and enhances cytotoxic T-cell-mediated lysis in EGFR-expressing tumor cells. 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. EGFR, belonging to the receptor tyrosine kinases family and upregulated or mutated in a variety of tumor cell types, plays a key role in tumor cell proliferation.
drug_mesh_term
Antibodies, Bispecific
drug_category
BISPECIFIC T ENGAGER
drug_class
Engager
drug_delivery_route
Intravenous
drug_mechanism_of_action
HLX35 is a bispecific IgG that binds EGFR on tumor cells and 4-1BB (CD137) on activated T/NK cells, crosslinking them to deliver tumor-localized 4-1BB costimulatory signaling while concurrently blocking EGFR signaling. This conditional 4-1BB agonism enhances T-cell proliferation, survival, and cytotoxicity, and can activate NK and dendritic cells, promoting antitumor immunity.
drug_name
HLX35
nct_id_drug_ref
NCT05442996