Preferred Label : Sovipostobart;
NCIt synonyms : Protease-activated Anti-CTLA-4 Antibody Prodrug BMS-986249; CTLA-4 Probody BMS-986249; CTLA-4-directed Probody BMS-986249;
NCIt definition : A probody composed of ipilimumab, a recombinant human immunoglobulin (Ig) G1 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 sovipostobart, 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-986249 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.;
UNII : U1OMP6W1PM;
CAS number : 2649371-19-5;
Molecule name : BMS-986249; BMS 986249;
NCI Metathesaurus CUI : CL544788;
Origin ID : C146765;
UMLS CUI : C5854755;
Semantic type(s)
- concept_is_in_subset
- has_target
