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

PGE2's Sneaky Sabotage: Alleviating PGE2 impairment of TIL expansion for effective adoptive Cell Therapy

PGE2's Sneaky Sabotage: Alleviating PGE2 impairment of TIL expansion for effective adoptive Cell Therapy

News @ Coukos Lab

Des chercheur-euse-s UNIL-CHUV dans "Highly Cited Researchers" 2023

Des chercheur-euse-s UNIL-CHUV dans "Highly Cited Researchers" 2023

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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)