Hi-TIDe | Human integrated tumor immunology discovery engine

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. 

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