Bio

Dr. Cheng joined UMKC in 2007 after receiving his Ph.D. in Pharmaceutical Sciences from the University of Tennessee Health Science Center. His research focuses on the development of novel therapeutics for liver fibrosis, breast cancer, prostate cancer, and pancreatic cancer. One of his major research interests is to use the phage display technology to discover peptides that can be used as ligands for tissue-specific drug delivery and tumor diagnosis. Dr. Cheng is a pioneer in discovering peptide-based immunotherapy agents using phage display. Accomplishments of Dr. Cheng’s research projects may provide evidence-based foundations for the development of anti-fibrotic agents and novel immunotherapies for various cancers. Dr. Cheng’s research has been continuously supported by Department of Defense (DoD), the National Institutes of Health (NIH), American Cancer Society (ACS), and the American Association of Pharmaceutical Scientists (AAPS). Dr. Cheng holds two US patents and is actively translating the technologies developed in his laboratory.

Abstract

Discovery of Anti-PD-L1 Peptides 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. Here, we discover peptide-based anti-PD-L1 inhibitors to block the PD-1/PD-L1 interaction. These peptides exhibit high affinity and specificity to human PD-L1 as well as PD-L1-positive human cancer cells. Molecular docking studies indicate that the CLP002 peptide specifically binds to PD-L1 at the site where PD-L1 interacts with PD-1. The CLP002 peptide inhibits tumor growth and increases survival of CT26 tumor-bearing mice, suggesting that the CLP002 peptide represents a promising low-molecular-weight checkpoint inhibitor for cancer immunotherapy.