Preferred Label : Anti-CTLA-4 Probody BMS-986288;
NCIt synonyms : Probody BMS-986288;
NCIt definition : A probody composed of a modified version of ipilimumab, a recombinant human monoclonal
antibody directed against the human T-cell receptor cytotoxic T-lymphocyte-associated
antigen 4 (CTLA4; CTLA-4), linked to a proprietary masking peptide that covers the
active antigen-binding site of the antibody through a protease-cleavable linker, with
potential immune checkpoint inhibitory and antineoplastic activities. Upon administration
of anti-CTLA-4 probody BMS-986288, the masking peptide is cleaved by tumor-associated
proteases upon extravasation into the tumor microenvironment (TME). Protease-mediated
removal of the linker enables binding of the unmasked monoclonal antibody moiety to
CTLA-4, which is expressed on certain T-cells. This inhibits the CTLA4-mediated downregulation
of T-cell activation, and leads to both activation of tumor infiltrating T-effector
cells and a cytotoxic T-lymphocyte (CTL)-mediated immune response against cancer cells.
CTLA4, an inhibitory receptor and member of the immunoglobulin superfamily expressed
on activated effector T-cells (Teffs) and regulatory T-cells (Tregs), plays a key
role in the inhibition of T-cell activity and downregulation of the immune system.
The peptide masking of BMS-986288 minimizes binding to CTLA-4 in normal tissues and
may reduce systemic toxicity, when compared to ipilimumab. Tumor-associated proteases
are present in high concentrations and aberrantly activated in the TME.;
Molecule name : BMS-986288; BMS 986288;
NCI Metathesaurus CUI : CL1407418;
Origin ID : C173435;
UMLS CUI : C5417982;
Semantic type(s)
- concept_is_in_subset
- has_target
