Low-molecular weight anti-PD-L1 peptide for cancer immunotherapy
Immunotherapy using checkpoint inhibitors, especially PD-1/PD-L1 inhibitors, has now evolved into the most promising therapy for cancer patients. However, most of these inhibitors are monoclonal antibodies, and their large size may limit their tumor penetration, leading to suboptimal efficacy. As a result, there has been a growing interest in developing low-molecular-weight checkpoint inhibitors.
UMKC investigators have developed small peptide-based anti-PD-L1 inhibitors, which exhibit high affinity and high specificity to human PD-L1 protein as well as PD-L1-positive human cancer cells. The best peptide shows high affinity to PD-L1 (KD=2.78 nM) and blocks the PD-1/PD-L1 interaction with an IC50 of 5 nM.
Compared to antibody, the peptide exhibits better tumor penetration in a 3D tumor spheroid model. The peptides inhibit tumor growth and increases survival of CT26 tumor-bearing mice. The newly discovered low-molecular weight anti-PD-L1 peptides can provide a more effective approach for cancer immunotherapy. They can also be used to construct bispecific checkpoint inhibitors for cancer immunotherapy.