anti-CTLA-4/anti-PD-1 monoclonal antibody combination BCD-217

A fixed dose combination of two monoclonal antibodies of which one is directed against the human negative immunoregulatory checkpoint receptor programmed cell death protein 1 (PD-1; PDCD1; CD279) and the other one is directed against the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4; CTLA-4), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, anti-CTLA-4/anti-PD-1 monoclonal antibody combination BCD-217 targets and binds to both PD-1 and CTLA-4 expressed on tumor-infiltrating lymphocytes (TILs) and inhibits the PD-1- and CTLA-4-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 CTLA-4 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 CTLA-4 enhances T-cell activation and proliferation more than the blockade of either immune checkpoint receptor alone.