Definition

A recombinant fusion protein comprised of a humanized immunoglobulin G1 (IgG1) antibody targeting the T-cell surface glycoprotein CD8 beta chain (CD8b) linked to an affinity-attenuated interleukin-2 (IL-2) mutein, with potential immunostimulating and antineoplastic activities. Upon administration of anti-CD8b antibody/IL-2 mutein fusion protein AB248, the antibody moiety specifically targets and binds to CD8+ T cells, thereby allowing for the IL-2 mutein moiety to specifically bind to IL-2R and activate IL-2R-mediated signaling in CD8+ T cells. This enhances cytotoxic T lymphocytes (CTLs)-mediated cytotoxic immune responses against tumor cells. The IL-2 mutein has a reduced affinity to IL-2 receptor subunit alpha (IL-2Ralpha; CD25) and beta (IL-2Rbeta; CD122), which promotes the selective activation of CD8+ T cells over natural killer (NK) cells and immunosuppressive regulatory T cells (Tregs). The IL-2Ralpha/IL-2R beta-mediated activation of NK cells and immunosuppressive Tregs is associated with immunosuppression and adverse effects including vascular leak syndrome (VLS).