Definition

A fusion protein composed of a monoclonal antibody directed against the immunosuppressive ligand programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274), fused with potency reduced interleukin (IL)-15/IL-15 receptor alpha (IL-15Ra) sushi domain complex, with potential immunostimulatory and antineoplastic activities. Upon administration of the anti-PD-L1/IL-15 fusion protein SIM0237, the anti-PD-L1 antibody moiety specifically targets and binds to PD-L1 expressing cells in the tumor microenvironment (TME). In turn, the IL-15/IL-15Ra complex stimulates the proliferation of natural killer (NK) cells, cytotoxic T lymphocytes (CTLs) and memory T cells locally in the TME, which induces an anti-tumor immune response. This may increase tumor cell killing and decrease tumor cell proliferation. PD-L1, a transmembrane protein, is expressed on the surface of antigen presenting cells (APCs) and on many cancer cell types. PD-L1 binding to PD-1, a negative regulator of the immune system on activated T cells, limits the expansion and survival of CD8-positive T cells, suppresses the immune system and results in immune evasion. IL-15 regulates CD8+ T and NK cell development, activation and proliferation. IL-15Ra complexed with IL-15 increases the half-life of IL-15. The attenuated IL-15 prevents the overstimulation of CD8+ T and NK cells.