Definition

A recombinant fusion protein consisting of a human monoclonal antibody directed against cytotoxic T-lymphocyte-associated antigen 4 (CTLA4; CTLA-4) fused to the immunostimulatory cytokine interleukin-15 (IL-15) cross-linked with the sushi domain of IL-15 receptor alpha (IL-15Ra), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration of anti-CTLA-4 monoclonal antibody-IL-15/IL-15Ra fusion protein JK08, the monoclonal antibody domain targets and binds to CTLA-4 expressed on T cells and inhibits the CTLA-4-mediated downregulation of T-cell activation. The IL-15/IL-15Ra complex targets and binds to CD8+ T and natural killer (NK) cells, thereby increasing their activation and proliferation. Altogether, this leads to an inhibition of regulatory T-cell (Tregs)-mediated immunosuppression, induces antibody-dependent cellular cytotoxicity (ADCC), increases memory T cells and enhances a cytotoxic T-lymphocyte (CTL)-mediated immune response against cancer cells. CTLA-4, an inhibitory receptor and member of the immunoglobulin superfamily (IgSF), plays a key role in the downregulation of the immune system.