Prof Coukos founded and directs the Hi-TIDe (Human Integrated Tumor Immunology Discovery Engine), an innovative research group, where discovery and technology development are pursued through team science.
Hi-TIDe is structured by design to comprise cutting-edge research laboratories with complementary missions and the necessary synergy to achieve impactful results.
The mission of Hi-TIDe is to develop effective individualised T-cell therapy approaches that can eradicate most solid tumors.
George Coukos conceived Hi-TIDe to develop solutions for two key challenges in cancer immunotherapy.
Development of universally applicable T cell therapy for all solid tumors
To address the first issue, George Coukos envisioned that T cells could be developed in most patients against tumor neoantigens, either canonical (i.e. derived from somatic mutations) or non-canonical (derived from any other tumor-specific molecular deregulation). Solutions to this daunting task required convergence of state-of-the-art antigen discovery and world class T cell development.
To this end, we have established cutting-edge methodologies in single-cell sequencing, proteogenomics computation and mass spectrometry immunopeptidomics to reliably identify tumor neoantigens at a high resolution in the group of Michal Bassani-Sternberg. In parallel, we have developed high throughput molecular and cellular methods for discovery of tumor-specific T cells that are actionable for personalized clinical therapy in the group of Alexandre Harari. We are also deepening our understanding of the molecular and cellular underpinnings of tumor immune recognition. Complementing these efforts, we are developing parallel approaches for off-the-shelf TCR and CAR engineered T cells in the group of Steven Dunn and that of Melita Irving.
Having reached such key milestones, the first generation of T cells directed against tumor neoantigens – the NEOTIL – are being tested in the clinic at the CHUV (link to service of ION, T cell clinical studies).
Overcoming tumor defences towards incoming T cells
This second challenge is immense, given the complexity of the tumor microenvironment (beyond what traditional experimental techniques can capture) and the capacity of tumors to adapt to therapeutic perturbations. George Coukos envisions that systems engineering, i.e. the convergence of systems approaches to immunology and the study of the tumor microenvironment, on the one hand, and systems-inspired sophisticated cell engineering on the other, will provide innovative solutions that can effectively eliminate solid tumors.
To this end, we apply systems immunology to unveil the states of human T cells in tumors and understand how these are determined by their microenvironment in the group of Dena Dangaj. In parallel, we apply structural and systems computational biology approaches to modify T cells for therapy) in the group of Jesus Corria Osorio. Our first generation Genetically Engineered for Enhanced Performance T (GEEP-T) cells are being tested preclinically, and soon to be so in the clinic.
The Hi-TIDe is part of the Center for Excellence in Cell Therapy, dedicated to developing innovative solutions for T cell therapy. A partnership between the CHUV/UNIL and the Ludwig Institute, the Center provides an end-to-end research-and-development and clinical translation environment for transferring novel cell therapy technologies to patients.
Learn more about the groups that make up the Hi-TIDe, under the leadership of Pr George Coukos.
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Judah Folkman Award from the Alliance for Cancer Gene Therapy (2006); The Sir William Osler Award for Excellence in Patient Oriented Research from the University of Pennsylvania (2006); the Kimmel Scholar Award from the Sidney Kimmel Foundation (2008); the NIH Roadmap, Director’s Transformative Award (2010); the Claudia Cohen Research Award for Ovarian Cancer (2012); the Advanced Grant award from the European Research Council (2013); and the Helga Salvesen Award for Best Translational Research, European Society of Gynaecologic Oncology (2019).
Pr George Coukos is Head of the Department of oncology UNIL CHUV, Director of the Lausanne Branch of the Ludwig Institute for Cancer Research's, and Head of the Service of immuno-oncology at the Lausanne University Hospital. He is equally co-director of the Swiss Cancer Center Léman, which he co-founded in 2016 with Pr Douglas Hanahan (EPFL) and Pr Pierre-Yves Dietrich (HUG and UNIGE).
He has a distinguished career with over 20 years' experience as both clinician and surgeon as well as leading investigator in the field of tumor immunology and immunotherapy. During his tenure at the University of Pennsylvania, Pr Coukos founded and directed the Ovarian Cancer Research Center, dedicated to translational research and development of innovative therapies for ovarian cancer, and served as Associate Director of the Division of Gynecologic Oncology.
His research work at Penn focused on elucidating fundamental mechanisms in the tumor microenvironment that determine the fate of antitumor immunity, especially the deregulation of tumor-infiltrating lymphocytes (TILs), with a translational focus largely concentrated on ovarian cancer. His laboratory discovered the presence of spontaneous antitumor immune response in ovarian cancer, disrupting the previous dogma that only few tumor types (e.g. melanoma or renal cell cancer) are immunogenic. It then characterized mechanisms driving TIL dysfunction at the tumor microenvironment. Among them, the role of tolerogenic myeloid cells, T regulatory cells, and notably tumor vasculature immune checkpoints. George Coukos was the first to propose the novel notion of the tumor endothelial barrier, i.e. that the vasculature actively controls T cell homing in tumors. Different molecular mechanisms were identified, offering novel therapeutic targets for cancer immunotherapy. Several clinical trials are presently ongoing, testing the combination of anti-angiogenesis drugs with immunotherapy by Coukos and others.
While at Penn, George Coukos played an active role translating novel lessons from the laboratory to the clinic through early phase clinical trials. Notably, he developed an autologous dendritic cell-based vaccine as well as adoptive T cell therapy with vaccine-primed autologous T cells in ovarian cancer. Currently, he is leading development and testing adoptive therapy with neoantigen-enriched tumor infiltrating lymphocytes in solid tumors.
In Lausanne, George Coukos established and directs the Hi-TIDe and the Center for Excellence in Cell Therapy, which are focused on developing and testing curative T cell therapies for solid tumors.
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