STUDY OF IMMUNE CELL BIOLOGY IN RESPONSE TO TREATMENT IN AML/MDS/WM PATIENTS

Preclinical development

Waldenström's macroglobulinemia

Immunotherapy

Preclinical research (TRL 4-5)

Analysis of lymphoid cells of the innate (NK) and adaptive (T) response in normal and in patients (AML, MDS, WM). Longitudinal studies before and after treatment of patients with immunotherapy or immunomodulating agents.

Measurement of the phenotypic and functional impact of the molecules used, alone or in combination, and over time, on the anti-leukemic potential of innate NK and adaptive T lymphocytes. Our experimental and analytical approaches combine the various parameters measured to provide an integrated picture of immune function following treatment.

Description

Scope of research activities

Preclinical/translational research using primary cells from healthy donors and patients (clinical trials, cohorts and observatories):

Studies of the phenotypic and functional profiles of Natural Killer cells
Checkpoint inhibitor studies
Phenotypic and functional analyses at different stages of the disease
Pre- and post-treatment phenotypic and functional analyses

Conducting the studies

Steps :

Study design for innovative products 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:

Access to primary cells from healthy donors via collaborations with clinical departments and Établissement français du sang (EFS)
Access to primary cells from AML, MDS and WM patients via collaborations with clinical departments in Paris

Specifications

The platform

Characterization of innate (NK) and adaptive (T) lymphoid cells from primary cell cultures.

Studies

Phenotyping of innate (NK) and adaptive (T) lymphoid cells in healthy donors and patients during disease progression.

Phenotypic characterization by flow cytometry
Cytokine assays (IFN-g, TNF-a)
Cytotoxic activity
Molecular analysis (multiplex qRT-PCR, RNA-seq)

Phenotyping of innate (NK) and adaptive (T) lymphoid cells in response to treatment.

Phenotypic characterization by flow cytometry
Cytokine assays (IFN-g, TNF-a)
Cytotoxic activity
Molecular analyses (multiplex qRT-PCR, RNA-seq)

Studies of drug cytotoxicity on immune cells (NK and T cells).

Cytokine assays
Cytotoxic activity
Molecular analyses (multiplex qRT-PCR, RNA-seq)
Metabolic analysis

Checkpoint inhibitor studies using primary human normal and leukemia cells.

Cytokine assays
Cytotoxic activity
Molecular analyses (multiplex qRT-PCR, RNA-seq)

Examples of partnerships

Biology of NK and T cells in response to treatment - Analysis of disease progression on NK and T cell phenotype in AML and MDS patients: pre- and post-treatment follow-up.

Partner: Sanofi R&D