FAPa-targeted CD40 agonist RO7300490

A CD40 agonist that targets the inducible tumor stromal antigen fibroblast activation protein-alpha (FAP-alpha; FAPa), with potential immunostimulatory and antineoplastic activities. Upon administration, FAPa-targeted CD40 agonist RO7300490 targets and binds to cell surface glycoprotein FAP which is broadly expressed on cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) of a variety of tumors. RO7300490 also binds to and activates CD40, a cell surface stimulatory receptor that belongs to the tumor necrosis factor (TNF) receptor family and is expressed on various immune cells, such as B lymphocytes, monocytes, and dendritic cells (DCs). This crosslinks FAP-expressing CAFs 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.