Human integrated tumor immunology discovery engine | Hi-TIDe

The Human Integrated Tumor Immunology Discovery Engine (Hi-TIDe) is an innovative multi-group research program of the Ludwig Branch Lausanne, where discovery and technology development are pursued through team science. It was founded and is directed by Pr George Coukos.

The Hi-TIDe is structured by design to comprise cutting-edge research teams with complementary missions and the necessary synergies to achieve clinically impactful results. 

The mission of Hi-TIDe is to develop effective individualised T cell therapy approaches that can eradicate most solid tumors.

We envision that effective immunotherapy can be developed for most patients leveraging natural tumor-infiltrating lymphocytes (TILs) or synthetic T cells, which can be rationally modified to overcome the barriers of the tumor microenvironment.

Development of universally applicable T cell therapies for solid tumors

Our first goal is to generate tumor-specific T cells. We take advantage of natural tumor-infiltrating lymphocytes (TILs) recognizing canonical (i.e. derived from somatic mutations) or non-canonical tumor neoantigens (derived from any other tumor-specific molecular deregulation). Solutions to this daunting task require the convergence of state-of-the-art antigen discovery and T cell methodologies.

The team of Michal Bassani-Sternberg has established cutting-edge methodologies in mass spectrometry immunopeptidomics and proteogenomics to investigate tumor neoantigens at a high resolution. In parallel, the team of Alexandre Harari has developed high throughput molecular and cellular methods to isolate and study tumor-specific T cells that are actionable for personalized clinical therapy.

Having reached such key milestones, we are testing the first generation of T cells directed against tumor neoantigens – the NeoTIL – in the clinic.  In the process, we are deepening our understanding of the molecular and cellular underpinnings of tumor immune recognition and are developing innovative methods and technologies for cancer immunotherapy.

Certain cancers harbour no actionable TILs or antigens. Complementing the above efforts, the teams of Steven Dunn and Melita Irving are developing parallel solutions for synthetic immunity including the development of tumor-directed immunomodulatory molecules and next generation chimeric antigen receptors.

Reprogramming tumor immunity

Overcoming tumor defences towards incoming T cells is an immensely complex but compelling mission. We envision that the convergence of systems immunology, to study the tumor microenvironment, and systems-inspired cell engineering, to rationally reprogram T cells, will provide the required solutions to effectively eliminate tumors.

We apply systems immunology to understand the tumor microenvironment and the associated states of T cells in tumors. The team of Denarda Dangaj analyses the tumor microenvironment as a whole to understand how tumors orchestrate immune deregulation and identify biomarkers of response to immunotherapy. In the team of George Coukos, we use systems biology approaches to unveil states of T cells in tumors and understand their molecular regulation, while we apply structural and systems computational biology to design T cell engineering for effective immunotherapy. Our first generation Genetically Engineered for Enhanced Performance T (GEEP-T) cells are being tested preclinically, and shortly in the clinic.

The Hi-TIDe is part of the Center of 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. 

Several development laboratories, the Center of Experimental Therapeutics and the clinical Service of Immuno-oncology are also part of the Center of Excellence in Cell Therapy.