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Lieping Chen, MD, PhD

United Technologies Corporation Professor in Cancer Research and Professor of Immunobiology, of Dermatology and of Medicine (Medical Oncology); Co-Leader, Cancer Immunology, Yale Cancer Center

Research Summary

My laboratory is interested in:

  1. T cell biology: Control of T cell response to antigens by cell surface receptors/ligands
  2. Cancer immunology: Mechanisms of tumor escape from immune attack in the tumor microenvironment
  3. Immunotherapy: Development of novel therapeutic approaches for human diseases (cancer, autoimmune diseases, inflammation etc.) based on our laboratory discoveries

Extensive Research Description

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

In 1999, Dr. Chen first to discover 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, he later showed that PD-L1 is highly upregulated in a fraction of human cancer and blocking the interaction between PD-1 and PD-L1 by monoclonal antibodies (mAbs) improved the immune system’s ability to eliminate tumors in a 2002. Chen’s work provided a foundation for the subsequent development of anti-PD-L1/PD-1 mAb-based immunotherapies. Dr. Chen also initiated and help organized the first-in-man clinical trial of anti-PD-1/PD-L1 mAbs for treating human cancer in and developed PD-L1 staining as a biomarker. His discoveries directly led to the development of anti-PD-1/PD-L1 antibody therapy against broad spectrum of human cancers, which become new standard for cancer treatment now.

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 to promote survival of effector T cells, leading to 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.

Coauthors

Research Interests

Immunotherapy; Inflammation; Medical Oncology; Neoplasms; Autoimmunity

Public Health Interests

Cancer; Immunology

Selected Publications