Hi-TIDe : T cell engineering

| Research interest | Research group projects | Selected Publications
 

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Melita IRVING
Group leader
Human integrated tumor immunology discovery engine (Hi-TIDe)

Department of oncology UNIL CHUV
Ludwig Institute for Cancer Research Lausanne

Phone +41 21 692 59 61
Fax +41 21 692 59 95
Email Melita.irving@unil.ch

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Research interest

Our research focuses on the development of gene-engineered T cells, tailored to treat specific tumors, that enable or promote:

  1. tumor-targeting
  2. productive T-cell signaling and metabolic activity under suppressive conditions
  3. tumor microenvironment (TME) re-programming to foster immunity
  4. safety

Research group projects

We have developed a variety of novel chimeric antigen receptors (CARs ; hybrid receptors that activate T cells upon tumor antigen binding), as well as T-cell receptors (TCRs), for T-cell engineering purposes, having strong clinical potential in terms of specificity, functionality and safety. We have also identified several promising molecules, both natural and rationally modified (and either expressed intracellularly or secreted) for improved in vivo tumor control and survival following the adoptive transfer of co-engineered TCR/CAR T cells (Figure 1). These molecules either directly promote T-cell activity and/or other protective immune infiltrate, and/or block/counteract various inhibitory mechanisms (low pH, cAMP, check-point ligands, etc.) in specific TMEs.

Moreover, important advances have been made by our group in vector design and T-cell transduction methodologies for improved gene-expression.

We have also developed a robust pre-clinical protocol for low-dose irradiation, rationally and optimally combined with immunotherapeutic drugs and antibodies based on TME characterization (gene-upregulation identified by Nanostring, qPCR, flow cytometry, immunohistochemistry etc.), for the treatment of advanced ovarian cancer which has been used as the rationale for a proposed clinical trial at the CHUV. Thanks to the Human-Tumor Immunology Discovery Engine (H-TIDE) platform, and close synergy between the CHUV-UNIL-SIB-EPFL, we have an unprecented opportunity to link patient bedside to benchwork & computer modeling in order to develop cutting-edge and powerful combinatorial immunotherapies to help cure patients. 

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Selected Publications

  • Irving M, et.al.,. 2017. Engineering CAR T-Cells for Racing in Solid Tumors; Don't Forget the Fuel. Front Immunol 8;267

  • Lanitis, E, et. al., 2017. Mechanisms regulating T-cell infiltration and activity in solid tumors. Ann Oncol.; in press

  • Santoro SP, et.al., 2014. T Cells Bearing a Chimeric Antigen Receptor against Prostate-Specific Membrane Antigen Mediate Vascular Disruption and Result in Tumor Regression. Cancer Immunol 3(1); 68-84

  • Irving M, et. al., 2012. Interplay between T cell receptor binding kinetics and the level of cognate peptide presented by major histocompatibility complexes governs CD8+ T cell responsiveness. J Biol Chem 287(27);23068-78

  • Irving M, et. al., 2010. Evidence for a TCR affinity threshold delimiting maximal CD8 T cell function. J Immunol 184; 4936-4946

Group members

 

  • Dimitrios ALATZOGLOU 
    PhD Student
  • Wilson CASTRO
    Research associate
  • Angel de Jesus CORRIA OSORIO
    Research associate
  • Elisabetta CRIBIOLI
    Research associate
  • Greta GIORDANO ATTIANESE
    Research Associate
  • Elise GRAY-GAILLARD
    Technician
  • Cristina JIMENEZ
    Postdoctoral Researcher
  • Evripidis LANITIS
    Research Associate
  • Paraskevas KOSTI
    Postdoctoral Researcher
  • Amandine MORIOT
    Technician
  • Tania MULLER
    Technician
  • Jennifer MURRAY
    Technician
  • Yaquelin ORTIZ MIRANDA
    PhD student
  • Khaoula OUCHEN
    Scholarship student
  • Julien PUJOL
    Technician
  • Patrick REICHENBACH
    Technician
  • Catherine RONET
    Research Associate
  • Kirsten SCHOLTEN
    Research Associate
  • Bili SEIJO
    Technician
  • Aikaterini SEMILIETOF
    Technician
  • Aodrenn SPILL
    Technician
  • Evangelos STEFANIDIS
    Research Associate
  • Romain VUILLEFROY DE SILLY
    Postdoctoral Researcher
  • Giulia D'ACCARDIO
    Intern
Ch. des Boveresses 155 - CH-1066 Epalinges
Switzerland
Tel. +41 21 692 59 92
Fax +41 21 692 59 95
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