CD80-Fc fusion protein KM602

A recombinant fusion protein composed of the extracellular domain (ECD) of human CD80 (B7.1) fused to a human immunoglobulin G1 (IgG1) Fc fragment, with potential immunostimulatory, immune checkpoint inhibitory and antineoplastic activities. Upon administration of CD80-Fc fusion protein KM602, the CD80 moiety targets and binds to CD28, which in the presence of antigenic T-cell receptor (TCR) signaling, leads to the co-stimulation of T-cell responses including the activation of naive and memory T cells. This leads to a cytotoxic T-lymphocyte (CTL)-mediated immune response against cancer cells, thereby killing cancer cells. KM602 also targets and binds to CTL-associated antigen 4 (CTLA4; CTLA-4), which prevents the binding of CTLA-4 to endogenous CD80 and enables CD80-CD28 engagement, CD28 signaling, and T-cell activation in the tumor microenvironment (TME). In addition, KM602 binds to the immunosuppressive ligand human programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274), which prevents the binding of PD-L1 to CD80 and enables CD80-CD28 engagement, CD28 signaling, and T-cell activation in the TME as well as abrogating the binding of PD-L1 to its receptor programmed cell death 1 (PD-1; cluster of differentiation 279; CD279) and preventing PD-L1/PD-1-mediated signaling, which further enhances an anti-tumor immune response. CD80 is a co-stimulatory molecule expressed on activated antigen presenting cells (APCs) that plays a key role in T-cell activation upon binding to CD28 on T cells. On the other hand, binding of CD80 to CTLA-4 prevents CD80-CD28 engagement, thereby inhibiting T-cell activity and immune activation, and T-cell exhaustion. CTLA-4, a member of the immunoglobulin superfamily (IgSF) and an inhibitory molecule, is upregulated by T cells following T-cell activation and plays a key role in the downregulation of the immune system. PD-1, found on activated T cells, negatively regulates T-cell activity; it plays a key role in immune evasion and prevents tumor cell lysis. PD-L1 is often overexpressed on tumor cell types and plays a key role in immune evasion.