OCT 06, 2016 9:00 AM PDT

Keynote Speaker - PD-1 cancer immunotherapy

Speaker
  • Professor of Medicine, Harvard Medical School
    Biography
      Gordon J. Freeman, PhD works in the Department of Medical Oncology at Dana-Farber Cancer Institute and is Professor of Medicine at Harvard Medical School. Dr. Freeman earned his BA in Biochemistry and Molecular Biology, and PhD in Microbiology and Molecular Genetics from Harvard University. His research has identified the major pathways that control the immune response by inhibiting T cell activation (PD-1/PD-L1 and B7-2/CTLA-4) or stimulating T cell activation (B7-2/CD28). In 2000, Dr. Freeman discovered PD-L1 and PD-L2, and showed they were ligands for PD-1, thus defining the PD-1 pathway and the drug target: block the interaction. He showed the function of PD-1 was to inhibit immune responses and that blockade enhanced immune responses. He showed that PD-L1 is highly expressed on many solid tumors such as breast and lung, as well as some hematologic malignancies and allows these tumors to inhibit immune attack. He received the 2014 William B. Coley Award for Distinguished Research in Tumor Immunology for this work that led to development of PD-1 pathway blockade for cancer immunotherapy.

    Abstract

    The immune system is capable of recognizing tumors and eliminates many early malignant cells. However, tumors evolve to evade immune attack, and the tumor microenvironment is immunosuppressive. Engagement of PD-1 by PD-L1 or PD-L2 results in attenuated TCR signaling and inhibition of T-cell immune functions.  Tumors exploit these immune checkpoint pathways to evade immune eradication. Blockade of the PD-1, PD-L1, and CTLA-4 checkpoints is proving to be an effective and durable cancer immunotherapy in a subset of patients in a broad variety of tumor types by allowing the patient to produce an effective anti-tumor immune response. Expression of PD-L1 by tumor cells or infiltrating immune cells correlates with responsiveness to PD-1 or PD-L1 blockade but is an imperfect biomarker since some patients who do not express PD-L1 still respond. A broad range of other immune modulatory targets has been identified and are potential targets for synergizing with immune checkpoint blockade. Advances in understanding T cell coinhibitory pathways have stimulated a new era of immunotherapy with effective drugs to treat cancer.
     


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