drug_type
RELEVANT_DRUG
intervention_type
Drug
drug_description
A humanized IgG1 anti-CTLA-4 monoclonal antibody checkpoint inhibitor (also known as ONC-392/BNT316); designed with pH-sensitive CTLA-4 binding to preserve peripheral CTLA-4 recycling while retaining Fc effector function to deplete intratumoral Tregs and enhance priming/expansion of tumor-reactive T cells; targets CTLA-4 and modulates the CD28–CD80/86 costimulation axis.
nci_thesaurus_concept_id
C173547
nci_thesaurus_preferred_term
Gotistobart
nci_thesaurus_definition
A humanized, pH-sensitive immunoglobulin (Ig) G1 monoclonal antibody directed against the human T-cell-expressed receptor cytotoxic T-lymphocyte-associated antigen 4 (CTLA4; CTLA-4; CD152), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, gotistobart targets and binds to CTLA-4 expressed on T-cells and inhibits the CTLA-4-mediated downregulation of T-cell activation. This leads to a cytotoxic T-lymphocyte (CTL)-mediated immune response against cancer cells, thereby killing cancer cells. As gotistobart is dissociated from CTLA-4 under low pH, it does not cause lysosomal degradation of CTLA-4, preserving CTLA-4 and allowing the recycling of CTLA-4. This may result in more efficient and selective CTLA-4-targeted regulatory T-cell (Treg) depletion within the tumor microenvironment (TME) while preserving CTLA-4 functions outside the TME, thereby reducing toxicities. CTLA-4, an inhibitory receptor and member of the immunoglobulin superfamily (IgSF), plays a key role in the downregulation of the immune system.
drug_category
INHIBITORY ANTIBODY
drug_class
Inhibitor
drug_delivery_route
Intravenous
drug_mechanism_of_action
Humanized IgG1 anti-CTLA-4 checkpoint inhibitor with pH-sensitive binding that preserves peripheral CTLA-4 recycling while retaining Fc effector function. Blocks CTLA-4 to relieve inhibition of CD28–CD80/86 costimulation, promoting priming/expansion of tumor-reactive T cells and selectively depleting intratumoral Tregs to enhance antitumor CTL responses with reduced systemic toxicity.
drug_name
Gotistobart
nct_id_drug_ref
NCT05671510