Mérieux Foundation event

Humanized models to study immunity and to accelerate the development of new solutions for human health

26 - 28 April 2017 - Les Pensieres Center for Global Health, Veyrier-du-Lac (France)

Summary

Translational research has emerged as one of the main pillars of the development of new vaccines or drugs over the past decade. It is indeed an absolute requirement for the pharmaceutical industries to better de-risk their candidates between preclinical proof of concept (PoC) in conventional animal models and the uncertain outcome of an efficacy study that usually takes place several years to a decade after, implying several hundreds of millions of dollars invested with a probability of success very often poorly controlled. A large number of parameters differ in the course of an immune response between laboratory animal models and human beings. Some of them are intrinsic to the host such as genetic polymorphism, metabolisms, physiology and specificities of the immune system (innate immune receptor distributions, differences in cell subset phenotype and functions, some variations in lymphatic or organic immune macro- and micro-architectures …). Others are environmental such as susceptibility or resistance to infections, co evolution of the host with the pathogen, impact of stress stimuli, role of the flora or of concomitant infections and immune history.

The development of new models to refine candidate selections has been the focus of many efforts to credentialize the preclinical PoC established in classical in vivo models such as laboratory mouse strains and non-human primates. This includes the use of simple to very sophisticated in vitro models based on human cells to test the potency of the compounds in vitro (from PBMCs in a well, to 3D cell cultures and organs on a chip). The latters, limited by their inherent in vitro attributes, have been nicely complemented by the development of animal models which have been humanized in order to better mimic the human responses so as to hopefully better predict outcomes in the targeted populations. Efforts towards the successful engraftment of human genes or gene loci first, of human hematolymphoid cells thereafter and finally of other human tissue cell types, started in the early 1990’s. Since then, the discovery and introduction of multiple targeted mutations into the host have continuously improved the quality and duration of such genetic, cellular and tissue engraftments.

The symposiums will be dedicated to the review of the most recent advancement in the development of such chimeric animal models and the impacts of the improvements of their humanization on the translation of new drug, mabs or vaccine candidates as well on the discovery of mode of actions, the identification of correlates of protection and of relevant biomarkers to human diseases, in the fields of oncology, autoimmunity, inflammatory and infectious diseases.

Program

Thursday, April 27

Friday, April 28

Session 1 New development for the construction of humanized mice

Jim DI SANTO

  • 8:30 - 8:50

    Generation of improved humanized mouse models for human infectious diseases

    Lenny SHULTZ

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  • 9:10 - 9:30

    Humanized mice to study human hematopoietic stem cells differentiation

    Claudia WASKOW

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  • 9:50 - 10:10

    Next generation humanized mouse models for normal and malignant hematopoiesis

    Alexandre THEOCHARIDES

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  • 11:00 - 11:40

    Key-note address: Genetic engineering of human hematopoiesis and its preclinical modeling in hematochimeric mice

    Luigi NALDINI

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Session 2 Humanized mouse models for the study of the physiopathology of infectious diseases

Nicolas BURDIN & Jacques LOUIS

  • 14:00 - 14:20

    Humanized mice to study the role of lymphocyte trafficking in HIV dissemination

    Maud DERUAZ

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  • 15:50 - 16:10

    Animal models of human oncogenic gamma-herpesvirus infection

    Christian MUNZ

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  • 17:10 - 17:30

    Application of humanized mice models in exploring novel therapy strategies against human diseases

    Jian ZHENG

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Session 3a) Humanized mouse models for the study of cancers development and therapy (personalized medicine). Tumors of the hemopoietic origin.

Alexandre THEOCHARIDES

  • 8:30 - 8:50

    The use of the AML xenograft model to translate leukemia stem cell biology to the clinic

    Jean WANG

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  • 9:10 - 9:30

    Humanized models to study myeloid malignancies

    Dominique BONNET

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  • 9:50 - 10:10

    A leukemia xenograft model that is representative of de novo drug resistant and very high risk ALL in NOD/SCID/gamma null mice

    Jean-Pierre BOURQUIN

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Session 4 Humanized mice models for the study of the human immune-induced diseases in humans

Jacques BANCHEREAU

  • 14:00 - 14:20

    A humanized mouse model to study insulin-specific tolerance and islet autoimmunity

    Carolin DANIEL

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