MOUSE MODELS FOR THE STUDY OF GRAFT-VERSUS-HOST DISEASE (GVHD) OR GRAFT-VERSUS LEUKEMIA (GVL) (ALL/AML)

Description

Scope of research activities

In vivo preclinical research using a mouse model mimicking patients with leukemia (AML and ALL) or lymphoma, treated by allogeneic transplantation, in the case of graft-versus-host disease or relapse: 

• Action mechanisms
• Targets identification and validation
• Drug screening
• Evaluation of therapeutic potential (i.e. efficacy) 
• Toxicity assessment (pre-regulatory)

Conduct of studies

Steps:

• Identification of relevant animal models according to the question raised, including models of acute or chronic GVH induced by major or minor antigenic incompatibilities, choice of the most relevant model of hematologic malignancies. 
• Definition of experimental conditions to test the hypothesis or scientific question, including the use of syngeneic controls or allogeneic T-cell-free transplants, and definition of response assessment modalities (small animal imaging, bioluminescence, conventional, confocal or biphotonic microscopy, flow or mass cytometry, global or single-cell transcriptomics) and relevant response markers.
• Preparation of regulatory applications for the implementation of animal experimentation after detailed writing of the experimental plan.
• Implementation of experiments following study planning, organization of interim meetings to monitor project progress and results.
• Final analysis and communication of results and conclusions

Research infrastructure 

Experimental and analytical platforms:

• Animal facility
• Cytometry, imaging and sequencing platform
• Cytometer and cell sorter available in the team
• Single-cell RNA sequencing using 10X genomics technology (CITE-seq, scRNA-seq, scATAC-seq, TCR-seq)
• A bioinformatics engineer to analyze results