In vivo drug screening platform accelerates anti-hCD40 antibody drug discovery
The CD40 (also known as TNFRSF5) and its ligand CD40L (also known as CD154) belong to the TNF/TNFR family. CD40 is expressed on antigen presenting cells (APCs), including B cell, monocytes, macrophages and dendritic cells. CD40-CD40L is a pair of costimulatory molecules that, after interacting at the cell surface, promotes intracellular signaling by recruiting TNFR-associated factor (TRAF) in the cytosol, thereby activating multiple downstream signaling pathways. Therapeutic targeting of CD40 by agonistic monoclonal antibodies (mAbs) aims to activate CD40+ APCs to effectively boost tumor-specific cytotoxic T cells to eliminate tumor cells. In principle it has the advantage of greater tumor specificity over other T cell activating approaches, such as checkpoint inhibition or indiscriminate T cell activation.