Definition

A mixture of the two engineered monoclonal antibodies iparomlimab, which is an immunoglobulin G4 (IgG4) monoclonal antibody directed against the human negative immunoregulatory checkpoint receptor programmed cell death protein 1 (PD-1; PDCD1; CD279) and tuvonralimab, which is an IgG1 monoclonal antibody directed against the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4; CTLA-4), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration of iparomlimab/tuvonralimab, iparomlimab and tuvonralimab target and bind to PD-1 and CTLA4 expressed on tumor-infiltrating lymphocytes (TILs), respectively. This inhibits the PD-1- and CTLA4-mediated downregulation of T-cell activation and proliferation. This restores immune function and activates a cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells. Both PD-1 and CTLA4 are selectively expressed on TILs in the tumor microenvironment (TME) and negatively regulate the activation and effector functions of T cells. They play key roles in the downregulation of the immune system and tumor evasion from host immunity. Dual checkpoint blockade of PD-1 and CTLA4 enhances T-cell activation and proliferation more than the blockade of either immune checkpoint receptor alone.