In vitro assay for the development of small molecule inhibitors targeting PD-1/PD-L1.

Cancer immunotherapy has recently emerged as one of the hot research field since clinical successes achieved by antibody drugs of immune checkpoints, among which PD-1 and its ligand PD-L1 are the well established molecules. PD-1/PD-L1 pathway induces immune tolerance and immune evasion, especially in tumor microenvironment, cancer cell is capable to escape the immune surveillance by up-regulating the expression level of PD-1 or PD-L1. Blockade of PD-1/PD-L1 can unleash the anti-tumor activity, and the strategy shows great successes in the treatment of various cancer types in the late stage. Beside antibody drugs, many other molecules such as peptides, high affinity PD(L)-1 mutants, chemical compounds, and DNA aptamers are designed for inhibitors of PD-1/PD-L1 pathway. Each modulators show their pros and cons based on their own physiochemical properties. Here we introduced the methods for identifying low molecular weight inhibitors of PD-1/PD-L1 and mainly discussed the cell-based blocking test.