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drug_type
RELEVANT_DRUG
intervention_type
Antibody-drug conjugate
drug_description
An anti-CD19 IgG monoclonal antibody–drug conjugate (Zynlonta; ADCT-402) that delivers the PBD dimer cytotoxic payload tesirine to CD19-expressing B cells. After binding and internalization, tesirine is released to create DNA interstrand crosslinks, triggering DNA damage responses, cell-cycle arrest, and apoptosis. Administered IV every 21 days for relapsed/refractory B-cell malignancies.
nci_thesaurus_concept_id
C125549
nci_thesaurus_preferred_term
Loncastuximab Tesirine
nci_thesaurus_definition
An antibody-drug conjugate (ADC) consisting of an anti-CD19 humanized monoclonal antibody conjugated, via a cleavable linker comprised of valine-alanine and maleimide, to a cytotoxic, cross-linking agent pyrrolobenzodiazepine (PBD) dimer, which targets DNA minor grooves, with potential antineoplastic activity. Upon administration, the monoclonal antibody portion of loncastuximab tesirine targets the cell surface antigen CD19 on various cancer cells. Upon antibody/antigen binding and internalization, the cytotoxic PBD moiety is released. The imine groups of the PBD moiety bind to the N2 positions of guanines on opposite strands of DNA. This induces interstrand cross-links in the minor groove of DNA and inhibits DNA replication, which inhibits the proliferation of CD19-overexpressing tumor cells. CD19, a transmembrane receptor and tumor-associated antigen (TAA), is expressed on a number of B-cell-derived cancers.
drug_mesh_term
loncastuximab tesirine
drug_category
ANTIBODY DRUG CONJUGATE
drug_class
Conjugate
drug_delivery_route
Intravenous
drug_mechanism_of_action
Humanized anti-CD19 monoclonal antibody linked via a cleavable linker to tesirine (a pyrrolobenzodiazepine dimer). After binding CD19 and internalization, the payload is released to form DNA minor-groove interstrand crosslinks (at N2-guanine), inhibiting DNA replication and inducing DNA damage response, cell-cycle arrest, and apoptosis in CD19-expressing B cells.
drug_name
Loncastuximab tesirine
nct_id_drug_ref
NCT05453396