DEVELOPMENT OF IMMUNOTHERAPIES TARGETING THE CYTOTOXIC ACTIVITY OF NK CELLS (ALL/MDS)
- Preclinical development
- AML
- MDS
- Immunotherapy
- Preclinical research (TRL 4-5)
3D model to study the cytotoxic activity of human NK cells for in vitro evaluation of new immunotherapies under conditions that mimic the complexity of the tumor environment.
By setting up three-dimensional interactions between the different cell types, the 3D model makes it possible to take into account the respective roles of immune and stromal cells in the development of an effective anti-leukemia response.
Description
Scope of research activities
Preclinical research using 3D in vitro models of MDS and AML:
- Screening
- Demonstration of mechanism of action
- Efficacy evaluation
Conduct of studies
Steps :
- Study design for innovative products designed to modulate anti-leukemic immune responses
- Organization, implementation and conduct of studies
- Drafting of study plans.
- Statistical analysis and interpretation of results
Research infrastructure
Experimental and analysis platforms:
- Cell cultures (lymphocyte or stromal populations)
- Spectral flow cytometry (40 simultaneous markers)
- Multiplex soluble molecule assay platform (Luminex)
- Fluorescence microscopy.
- Bioinformatics data analysis pipelines (flow cytometry, RNA-seq, etc.)
Biological resources:
- 3D medullary organoid model.
Specifications
The platform
Screening platform using 3D in vitro models (co-culture of stromal cells/mesenchymal strains, blast cells, NK cells from patients, healthy donors or lines depending on the question asked) to mimic the complexity of the tumor environment.
Studies
Screening of drug candidates targeting the anti-leukemic activity of NK cells:
- Cytokine assays (IFN-g, TNF-a)
- Cytotoxic activity
Evaluation of the activity of drug candidates on the anti-leukemic action of NK cells:
- Cytokine assays (IFN-g, TNF-a)
- Cytotoxic activity
Mechanism of action of drug candidates on the anti-leukemic activity of NK cells:
- Cytokine assays (IFN-g, TNF-a)
- Cytotoxic activity
- Molecular analyses (multiplex qRT-PCR, RNA-seq)