While at the University of Washington, St. Louis, Prof. Dustin led a collaborative group in discovering requirements for the T-cell immunological synapse. He then moved to the Skirball Institute of Biomolecular Medicine at New York University School of Medicine, where he collaborated on new intravital microscopy projects. Continuation of work on the immunological synapse led to a basic description of the supramolecular assemblies that make up the mature immunological synapse. Specialized functions of the immunological synapse in cytotoxic T-cells and regulatory T-cells were also explored. This work includes the recent observation that the small vesicles enriched in T-cell receptor, synaptic ectosomes, are directly budded into the immunological synapse, handing off T-cell receptor and other cargo to the antigen presenting cell. He was director of the NIH funded Nanomedicine Center for Mechanobiology from 2009-2014 In order to further advance studies on the immunological synapse and translation to treatment of human diseases he moved to the Kennedy Institute of Rheumatology at the University of Oxford in 2013.
Dr. Fridman's research interests have been focused around the role of the immune system in controlling human tumors and the biological functions of receptors for IgG antibodies, both through basic and translational approaches. His team identified the protein references which trigger the biological functions of the receptors for IgG. He first demonstrated an immune response of the patient to his own cancer in acute leukemia. He then focused on the analysis of the tumor microenvironment with the demonstration of the beneficial effect of a Th1-oriented immune response to control clinical outcome in cervical cancer. His studies have changed the paradigm of host/cancer interactions by demonstrating that the "immune contexture", taking into account the functionality, the location, and the density of the immune infiltrate in colorectal tumors, is the major prognostic factor for human cancers.
Dr. Gajewski investigates and develops new treatments for patients with melanoma. He has a special interest in the development of immunotherapies against this disease. Dr. Gajewski also leads development of immune-based therapies for other cancers, using new laboratory data on how the immune system is regulated to develop novel clinical trials. He serves as an editor for Cancer Research and Journal for Immunotherapy of Cancer. In addition, he is immediate past president of the Society for Immunotherapy of Cancer and has served on the program committees for the American Society for Clinical Oncology (ASCO) and the American Association for Cancer Research (AACR).
Stephan Grupp, M.D., Ph.D., is the Chief of the Cellular Therapy and Transplant Section, Director of the Cancer Immunotherapy Program, and Director of Translational Research in the Center for Childhood Cancer Research at the Children's Hospital of Philadelphia (CHOP), and the Yetta Dietch Novotny Professor of Pediatrics at the University of Pennsylvania. A bone marrow transplant physician, he is a member of the Division of Oncology and the Medical Director of the Cell and Gene Therapy Lab. He has been a member of the National Academy of Medicine since 2019. His primary area of clinical research is the use of CAR T and other engineered cell therapies in relapsed pediatric cancers. He led all of the pediatric ALL trials of CTL019 (now approved as Kymriah), including the largest and most successful engineered T-cell therapy clinical trial conducted to date, as well as the global registration trial for CTL019. As a result of this work, he presented the Clinical Perspective at the July 2018 FDA ODAC meeting, at which reviewers voted 10-0 for recommendation of approval for Kymriah in pediatric ALL. His primary laboratory interest is the development of new cell therapy treatments for pediatric cancers.
Sewell group research is focused around T-cell ligands and the receptors that recognise them (αβTCR, γδTCR, CD4 and CD8). Most of our work is based around understanding the basic biology of antigen recognition by human T-cells and we have developed two working, unpublished pipelines for the discovery of new T-cell targets. We also collaborate with various partners to undertake translational projects. Areas of interest include: Dissection of successful immune responses after adoptive transfer of Tumour Infiltrating Lymphocytes; TCR gene transfer therapy; New CAR-T technologies; Artificial (non-biologic) T-cell antigens as vaccines; T-cell/TCR-based diagnostics in autoimmune disease; and, Unconventional (non-HLA-restricted) T-cell responses to infection and tumours.
Dr. Mario Sznol is a Professor of Medicine (Medical Oncology). Dr. Sznol, formerly with the National Cancer Institute, has an international reputation in cancer drug development. Dr. Sznol's expertise and experience is in cancer immunotherapy, drug development for cancer, and treatment of patients with melanoma and renal cell carcinoma. He is working to expand the opportunities for clinical trials at the Yale Cancer Center, particularly those focusing on immunotherapy and novel agents.