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  • 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, anti-CTLA-4 monoclonal antibody ONC-392 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 ONC-392 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.
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