Preferred Label : Anti-B7-H3/PD-L1-P1003 Bispecific Antibody-drug Conjugate DB-1419;
NCIt synonyms : Anti-PD-L1/Anti-B7-H3 ADC DB-1419; B7-H3xPD-L1-targeting BsADC DB-1419; Anti-B7-H3/PD-L1 ADC DB-1419; Anti-B7-H3/PD-L1 Antibody-drug Conjugate DB-1419; Anti-B7-H3/Anti-PD-L1 ADC DB-1419;
NCIt definition : A bispecific antibody-drug conjugate (ADC) composed of a bispecific humanized immunoglobulin
G1 (IgG1) antibody directed against the tumor associated antigens (TAAs) B7-homologue
3 (B7-H3, CD276) and the immunosuppressive ligand programmed cell death-1 ligand 1
(PD-L1; cluster of differentiation 274; CD274), conjugated, via a cleavable linker
containing maleimide tetrapeptide, to the cytotoxic DNA topoisomerase I inhibitor
P1003, with potential antineoplastic and immunomodulating activities. Upon administration,
anti-B7-H3/PD-L1-P1003 bispecific ADC DB-1419 targets and simultaneously binds to
B7-H3 and PD-L1 expressed on tumor cells. Upon binding, internalization and linker
cleavage, P1003 is released and inhibits DNA topoisomerase I activity, thereby inhibiting
DNA replication and resulting in cell cycle arrest and tumor cell apoptosis in B7-H3-
and PD-L1-expressing tumor cells. The binding of DB-1419 to PD-L1 also prevents the
interaction between PD-L1 and its receptor programmed cell death 1 (PD-1; cluster
of differentiation 279; CD279) on activated T-cells. This reverses T-cell inactivation
caused by PD-1/PD-L1 signaling and enhances the cytotoxic T-lymphocyte (CTL)-mediated
anti-tumor immune response against PD-L1-expressing tumor cells. DB-1419 is also able
to cause antibody-mediated antibody-dependent cellular cytotoxicity (ADCC), thereby
further killing tumor cells. In addition, DB-1419 causes a bystander effect, thereby
further killing both B7-H3- and PD-L1-positive and B7-H3- and PD-L1-negative tumor
cells. B7-H3, a type I transmembrane protein and a member of the B7 co-stimulatory
protein superfamily, is overexpressed on certain tumor cell types and on various immune
cells. It is an immunoregulatory protein and negative regulator of T-cell activation
and its overexpression plays a key role in tumor cell invasion and metastasis. PD-L1,
which is overexpressed in many human cancer cell types, plays an important role in
the downregulation of the immune system and tumor evasion from host immunity. PD-L1
binding to PD-1 suppresses the immune system and results in immune evasion.;
Molecule name : DB-1419; DB 1419;
Origin ID : C218470;
concept_is_in_subset
- has_target
