The PD1-CD40 human bispecific antibody YH008 demonstrates: • Activation of CD40 signaling in a PD1-dependent manner in vivo. • Superior in vivo efficacy against B16F10 and PDL1-CD40 BsAb treatment. • Increased percentage of CD8+ T cells and activation of dendritic cells in the tumor microenvironment. • No signs of systemic toxicity when administered in high doses.