Definition

An agent targeting both the tumor-associated antigen (TAA) fibroblast activation protein (FAP) and CD40, with potential immunostimulatory and antineoplastic activities. Upon administration, FAP/CD40-targeting agent SHR-7367 targets and binds to both FAP, localized predominantly on cancer-associated fibroblasts (CAFs) in the tumor stroma, and CD40, a cell surface stimulatory receptor expressed on various immune cells including B lymphocytes, monocytes and dendritic cells (DCs). The simultaneous binding to FAP and CD40 results in local clustering of FAP-expressing tumor stromal cells and CD40-expressing immune cells. Activation of CD40 induces proliferation and activation of B lymphocytes, shifts the induction of suppressive macrophages towards immunostimulatory macrophages, activates monocyte-derived DCs (moDCs), and leads to the secretion of inflammatory cytokines, which activates the immune system to induce the proliferation and activation of cytotoxic T lymphocytes (CTLs) against tumor cells. CD40, a member of the tumor necrosis factor receptor superfamily (TNFRSF), plays a key role in the activation of the immune system. FAP is abundantly expressed by CAFs in many solid tumors.