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drug_type
RELEVANT_DRUG
intervention_type
Drug
drug_description
A humanized monoclonal antibody–drug conjugate targeting DLK1; after binding DLK1 on tumor cells, it is internalized and releases a cytotoxic payload to induce targeted tumor cell death. Evaluated in DLK1-expressing neuroendocrine neoplasms and adrenocortical carcinoma.
nci_thesaurus_concept_id
C201679
nci_thesaurus_preferred_term
Anti-DLK-1 Antibody-drug Conjugate ADCT-701
nci_thesaurus_definition
An antibody-drug conjugate (ADC) composed of HuBa-1-3D, a humanized immunoglobulin G1 (IgG1) monoclonal antibody directed against human delta-like 1 homolog protein (DLK-1; DLK1) and site-specifically conjugated to PL1601, which contains a valine-alanine cleavable linker and SG3199, a cytotoxic pyrrolobenzodiazepine (PBD) dimer, with potential antineoplastic activity. Upon administration of anti-DLK-1 ADC ADCT-701, the antibody moiety targets and binds to DLK-1, which is expressed on the surfaces of a variety of cancer cell types. Upon endocytosis and enzymatic cleavage by cathepsin, free PBD is released and forms highly cytotoxic DNA interstrand cross-links, thereby blocking cell division and killing DLK-1-expressing cancer cells. DLK-1, an epidermal growth factor (EGF)-like membrane bound protein overexpressed by certain tumor cell types and on certain cancer stem cells (CSCs), plays a key role in tumor cell proliferation. Its expression is widely expressed during fetal development but in adult healthy tissue it is very restricted.
drug_mesh_term
Antibody-Drug Conjugates
drug_category
ANTIBODY DRUG CONJUGATE
drug_class
Conjugate
drug_delivery_route
Intravenous
drug_mechanism_of_action
Humanized IgG1 antibody targeting DLK1 linked via a cleavable linker to a pyrrolobenzodiazepine (PBD) dimer; after binding DLK1 on tumor cells, the ADC is internalized and cathepsin-mediated cleavage releases the PBD payload, which creates DNA interstrand cross-links, inhibiting cell division and killing DLK1-expressing cancer cells.
drug_name
ADCT-701
nct_id_drug_ref
NCT06041516