Programmed Cell Death-1 (PD-1) blockade inhibits the interaction between PD-1 and its receptors PD-L1/L2. PD-L1 blockade fails to address the engagement between PD-L2 and PD-1. Bispecific antibodies (BsAbs) provide dual ligand specificity, allowing blockade of PDL1/2. I compared the efficacy and specificity of BsAbs with clinical anti-PD-L1 antibodies, and their in vivo efficacy. PD-L1/L2 BsAbs promote ADCC activity against target cells expressing PDL1/2.  BsAbs possess higher in vivo efficacy in a mouse colon cancer model.