Binding agents that specifically bind the extracellular domain of human TIGIT and methods of use are disclosed. The binding agents may comprise a soluble poliovirus receptor (PVR) variant with one or more amino acid substitutions as compared to wild-type PVR. Binding agents may specifically bind the extracellular domain of human TIGIT and do not bind or bind weakly to the extracellular domain of human CD226, which can be used in the methods for the treatment of diseases such as cancer.