Hi-TIDe : T cell systems engineering

Coukos Lab

Our focus

Our group focuses on engineering T cell states that are associated with immune rejection in cancers. We employ systems biology approaches to study molecular T cell states associated with deregulation or immune attack either at the steady state or following T cell therapy in the human and in mouse. Learning from such lessons, we engineer and reprogram tumor-specific T cells to achieve superior performance and tumor elimination,

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Our projects

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  • We use systems biology approaches to decipher the molecular T cell states associated with successful immune attack or immune failure in human and mouse tumors.
  • In collaboration with Hi-TIDe’s Tumor microenvironment & biomarkers group and T cell discovery group, we capture tumor-infiltrating lymphocytes in human tumors in action, at the steady state or following adoptive T-cell therapy and other therapeutic perturbations, and interrogate them exhaustively to unveil the underlying T cell intrinsic signaling regulatory networks.
  • Departing from prior knowledge and the above observations, we design novel synthetic T cell states, aspiring to overcome tumor immune resistance and T cell deregulation in order to defeat difficult cancers.
  • We have developed the first generation GEEP-TTM (or Genetically Engineered for Enhanced Performance T) cells through orthogonal combinatorial engineering, i.e. introducing in therapeutic T cells desirable properties, such as stemness and cytotoxicity. We discovered that perturbations introduced in  GEEP-T reprogrammed adoptively transferred T cells into new states conducive to tumor control without the need for host lymphodepletion .
  • We characterize novel synthetic T cell states at the epigenetic, transcriptional, proteomic, and metabolomic level to infer new genetic perturbations with the potential to improve T cell antitumor efficacy.
  • Using genetic screens along with mathematical modelling, we seek  to understand and rationally manipulate CD8 T cell fate decisions. We seek to develop computational tools to reconstruct the transcriptional gene regulatory network underpinning CD8 T cell states, in order to further guide T cell engineering.
  • We move our novel T cell technologies to the bedside, in collaboration with the other groups in the Hi-TIDe, the Center of Excellence for Cell Therapy, the Center of Experimental Therapeutics and the Service of immuno-oncology.

News @ Coukos Lab

Four members of the Department of oncology UNIL CHUV named to Clarivate Analytics’ Highly Cited Researchers 2021

Four members of the Department of oncology UNIL CHUV named to Clarivate Analytics’ Highly Cited Researchers 2021

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CONTACT

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George COUKOS
Full Professor
Ludwig member

- Director of Hi-TIDe - Human integrated tumor immunology discovery engine
- Head of the Department of oncology
- Director of Ludwig Institute for Cancer Research Lausanne

Department of oncology UNIL CHUV
Ludwig Institute for Cancer Research Lausanne

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Phone +41 21 314 0627
E-mail

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Ch. des Boveresses 155 - CH-1066 Epalinges
Switzerland
Tel. +41 21 692 59 92
Fax +41 21 692 59 95
Ludwig Cancer ResearchUniversité de LausanneCentre Hospitalier Universitaire Vaudois (CHUV)