In recent years, monoclonal antibodies have been successfully used in clinical trials to block or activate key mediators of immune checkpoint pathways, including CTLA4,PD-1, PD-L1,CD40 and others. Combination therapy can promote antigen release and T cell priming, Tcell activation and homing, which helps to overcome tumor immune- evasive mechanisms and maximize efficacy, ultimately benefitting most patients.However, along the lO drug development process,in vivo efficacy models have always been arate-limiting step, especially to test combination therapy using two lO antibodies.The transmembrane protein receptor CD40 is a member of the tumor necrosis factor (TNF) receptor super family and is involved in costimulation of immune cells.