Lieping Chen, MD, PhD

In 1992, Dr. Lieping Chen showed the first proof-of-concept study that the B7-CD28 family molecules could be targets for cancer immunotherapy. This study inspired subsequent research targeting the B7-CD28 family molecules for the treatment of human cancer.

In 1999, Dr. Chen first discovered a molecule he called B7-H1 (also known as PD-L1). He subsequently showed that PD-L1 is expressed by tumors and that its activity can cause T cell dysfunction, thus preventing T cells from eliminating cancer cells in the tumor microenvironment. Bringing these lines of inquiry full circle, Lieping later showed that PD-L1 is highly upregulated in a fraction of human cancers, and blocking the interaction between PD-1 and PD-L1 by monoclonal antibodies (mAbs) improved the immune system’s ability to eliminate tumors. Chen’s work provided a foundation for the subsequent development of anti-PD-L1/PD-1 mAb-based immunotherapies. Dr. Chen also initiated and facilitated the first-in-human clinical trial of anti-PD-1/PD-L1 mAbs for treating human cancer and developed PD-L1 staining as a biomarker for these treatments. His discoveries directly led to the development of anti-PD-1/PD-L1 antibody therapy against a broad spectrum of human cancers, which became the new standard for current cancer treatment.

Other findings made by Dr. Chen's laboratory include the development of an agonist antibody against the 4-1BB (also known as CD137) co-stimulatory pathway to costimulate and promote survival of effector T cells, leading to the elimination of established tumors in mouse models. These findings have since been developed and are now being evaluated in clinical trials for human cancer. Dr. Chen’s laboratory also discovered various molecular pathways with T cell costimulatory and coinhibitory functions and/or their applications in human disease treatment. These pathways include B7-H2 (ICOSL), B7-H3, B7-H4, B7-H5/CD28H, PD-1H (VISTA), TNFRSF19, RELT, LIGHT/HVEM, B7-H2/CD28/CTLA-4 (human), SALM5/HVEM, FGL1/LAG-3, Siglec-15, etc. Many of these findings are now being developed clinically for the treatment of human cancer, autoimmune diseases, and inflammation.