PROJECT DESCRIPTION
CAR-T cell therapy is entering a major new phase with the emergence of in vivo engineering strategies, which could substantially reduce treatment costs, manufacturing complexity and time to treatment. Different CAR delivery strategies are being proposed, generally within two main categories, viral and non-viral approaches, each presenting benefits and downsides. Nonetheless, efficiency and specificity of vector delivery remain a main challenge. In this project we will first develop and optimise complementary viral and non-viral platforms for in vivo CAR delivery. These delivery systems will then undergo comparative evaluation in a unique set of predictive preclinical models, comprising humanized mice and a patient-derived organotypic platform that preserves native human tissue architecture and the tumor microenvironment. This integrated framework will enable systematic assessment of the major questions facing in vivo CAR-T development, including delivery efficiency, cellular specificity, biodistribution, off-target transduction, safety and functional efficacy. In parallel, pharmacological strategies will be adapted to improve in vivo CAR-T cell production and the fitness and anti-tumor function of in vivo-generated CAR-T cells.
EXPECTED PROFILE
We are looking for a highly motivated M2 candidate, willing, in principle to pursue this work with a PhD Thesis. Essential requirements:
- Willingness to work with mice models
- Grade average allowing to envisage submitting a candidature to doctoral schools
Additional experience in the following topics would be an advantage:
- Interest, and preferably previous knowledge in immunology, cancerology or virology
- Practical experience in viral production and primary cell cultures
- Practical experience in flow cytometry
CONTACTS
Equipe Mangeney
Marianne.mangeney@gustaveroussy.fr
Maude.marchais@gustaveroussy.fr
Equipe Donnadieu: