Lieping Chen, MD, PhD

My research focuses on identifying novel cell surface and secreted proteins that govern T cell activation, tolerance, memory, and survival. My career is also dedicated to translating fundamental laboratory discoveries into transformative therapies, primarily in cancer immunotherapy. In 1992, my laboratory published the first proof-of-concept study demonstrating that manipulating the B7-CD28 family, specifically by introducing B7-1 into tumor cells, could enhance anti-tumor immunity.

In 1999, my laboratory discovered the B7-H1 (PD-L1) molecule and was the first to establish the PD-1/PD-L1 pathway as a mechanism of immune evasion within the tumor microenvironment (TME). These foundational findings led me to co-initiate the first-in-human clinical trial of PD-1/PD-L1 blockade in 2006. We further pioneered the use of PD-L1 tumor tissue staining as a predictive biomarker, a contribution that directly informed the FDA approval of anti-PD-1/PD-L1 antibodies and redefined the standard of care across multiple cancers. My central hypothesis, that the TME is the primary site of immune evasion, remains a cornerstone of contemporary tumor profiling and drug discovery.

Beyond the PD-1/PD-L1 axis, my laboratory has identified over 20 novel immune modulators, including 4-1BB, ICOS/B7-H2, B7-H3, B7-H4, B7-H5/CD28H, PD-1H, LIGHT/HVEM, FGL1/LAG-3, Siglec-15, CD93/IGFBP7, and CD8a/PILRa. By discovering their mechanisms of action and therapeutic potential, we have catalyzed broad therapeutic development programs across academia and industry. Several of these targets are now in advanced clinical stages: 4-1BB agonists and B7-H4 antibodies are in Phase I/II trials; B7-H3 is a target for ADCs, bispecific T cell engagers, and CAR-T therapies (Phase I-III); and Siglec-15 and CD93 antibodies have reached Phase II.