CD274 and cancer: Several mAbs targeting PD-1 and PD-L1 have achieved FDA approval for the treatment of cancer (37, 38), but they suffer from a number of drawbacks, such as low tumor tissue permeability, potential immunogenicity associated with the protein nature (10, 39, 40), immune-related adverse effects (41), low modularity, low-temperature stability, development of resistance and high cost (one checkpoint blockade treatment for a single patient costs approximately $1 million (14)).