Definition

A humanized immunoglobulin G1 (IgG1) bispecific antibody targeting both the tumor-associated antigen (TAA) human epidermal growth factor receptor 2 (HER2; ErbB2; HER-2) and the costimulatory receptor 4-1BB (CD137; tumor necrosis factor receptor superfamily member 9; TNFRSF9), with potential immunostimulating and antineoplastic activities. Upon administration, anti-HER2/4-1BB bispecific antibody YH32367 simultaneously targets and binds to HER2 expressed on tumor cells and 4-1BB expressed on activated T lymphocytes and natural killer (NK) cells. This crosslinks HER2-expressing tumor cells and 4-1BB-expressing T cells and NK cells, and activates 4-1BB signaling locally in the tumor microenvironment (TME). This results in cytotoxic T-cell co-stimulation and enhances T-lymphocyte-mediated anti-tumor activity. YH32367 also promotes the secretion of interferon-gamma (IFNg) from T cells, which leads to tumor cell lysis. In addition, the binding of YH32367 to HER2 prevents HER2-mediated signaling. This inhibits the proliferation of HER2-expressing tumor cells. HER2 is overexpressed in a variety of cancer cell types and is associated with increased tumor cell proliferation. 4-1BB, a surface glycoprotein of the tumor necrosis factor receptor superfamily, is an inducible costimulatory receptor that plays a key role in T-cell proliferation, survival and cytolytic activity.