Hi-TIDe : T cell engineering

IRVING Lab

Our focus

Our main research interest is the development of tumor-directed TCR- and CAR T cells that are programmed to logically respond to microenvironmental cues or/and small molecule administration for maximized function, fitness and safety. We have optimized retroviral, lentiviral and CRISPR-Cas9 based tools and methodologies, as well as T-cell expansion conditions, allowing efficient evaluation of next-generation T cells in the context of both syngeneic and xenograft tumor models.

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Our projects

  • We have optimized the transduction and expansion of murine CAR T cells for cancer immunotherapy (DOI: 10.1084/jem. 20192203). We are now using these tools to evaluate logic-based, next generation CAR designs for the treatment of syngeneic solid tumors in the context of a fully competent immune system. 
  • In collaboration with Pr Olivier Michielin, Dr Michel Cuendet and Pr Vincent Zoete we are comparing the efficacy of computationally designed TCRs (DOI: 10.1074/jbc. M112.357673) and of small molecule responsive T-cell-signaling mediators for improved tumor control and safety.
  • In collaboration with Pr Bruno Correia (EPFL), we have developed a novel STOP- CAR that can be remotely controlled by administration of a small molecule (DOI: 10.1038/s41587-019-0403-9). We are currently evaluating additional STOP-switch designs, as well as a novel ON-switch responsive to clinically approved molecules, for enhanced safety, as well as improved function via abrogation of CAR-T-cell exhaustion.

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  • We have recently demonstrated that the function of VEGR-2 targeted CAR T cells is impaired by competition with soluble VEGF-A (JITC). We aim to elucidate factors in the solid tumor microenvironment that can inhibit CAR T cells and develop decoys/traps or signaling switch receptors to rescue/enhance their activity.

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KEY PUBLICATIONS

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CONTACT

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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

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Phone +41 21 692 59 61
Fax +41 21 692 59 95
E-mail

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CONNECT WITH ME

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Featured Publication -------

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Optimized gene engineering of murine CAR-T cells reveals the beneficial effects of IL-15 coexpression
Feb-2021 | Evripidis Lanitis...Melita Irving

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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 Research Université de Lausanne Centre Hospitalier Universitaire Vaudois (CHUV)