Skip to main content
drug_type
RELEVANT_DRUG
intervention_type
monoclonal antibody
drug_description
TIGIT-targeting IgG1 monoclonal antibody with intact Fc; blocks TIGIT binding to CD155 (PVR) and CD112 (Nectin-2) to relieve TIGIT-mediated suppression, enhance CD8+ T-cell activity, and leverage Fc effector function for NK cell-mediated depletion of TIGIT-high intratumoral Tregs.
nci_thesaurus_concept_id
C184307
nci_thesaurus_definition
A humanized immunoglobulin G1 kappa (IgG1k) monoclonal antibody targeting the co-inhibitory molecule and immune checkpoint inhibitor T-cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains (TIGIT), with potential immune checkpoint inhibitory activity. Upon administration, lancastotug targets and binds to TIGIT expressed on various immune cells, particularly on tumor-infiltrating lymphocytes (TILs) and natural killer (NK) cells, thereby preventing the interaction of TIGIT with its ligands CD112 (nectin-2; poliovirus receptor related-2; PRR2; PVRL2) and CD155 (poliovirus receptor; PVR; nectin-like protein 5; NECL-5). This enhances the interaction of CD112 and CD155 with the costimulatory receptor CD226 (DNAX Accessory molecule-1; DNAM-1), which is expressed on immune cells, such as NK cells and CD8+ T-cells. This leads to CD226 dimerization and CD226-mediated signaling and activates the immune system to exert a T-cell-mediated immune response against cancer cells. TIGIT, a member of the Ig super family (IgSF) and an immune inhibitory receptor, plays a key role in the suppression of T-cell proliferation and activation; it is involved in tumor cell immune evasion, and the inhibition of antiviral immune responses.
drug_category
INHIBITORY ANTIBODY
drug_class
Inhibitor
drug_delivery_route
Intravenous
drug_mechanism_of_action
Humanized IgG1 anti-TIGIT immune checkpoint antibody that blocks TIGIT interaction with CD155 (PVR) and CD112 (Nectin-2), restoring CD226 co-stimulatory signaling and enhancing CD8+ T-cell and NK-cell activity; intact Fc enables ADCC/ADCP to deplete TIGIT-high intratumoral Tregs.
drug_name
AK127
nct_id_drug_ref
NCT05868876