IN VITRO TRANSLATIONAL STUDIES FOR THE DEVELOPMENT OF DIFFERENTIATING TARGETED THERAPIES FOR ACUTE MYELOID LEUKEMIA

Preclinical development

Targeted therapy

Preclinical research (TRL 4-5)

In vitro translational studies to evaluate new differentiating targeted therapies for the treatment of acute myeloid leukemia (AML).

UMR-1170 works closely with Gustave Roussy's Department of Therapeutic Innovation and Early Trials (DITEP), which has expertise in hematology and whose missions are to offer patients in therapeutic failure access to innovative molecules and to accelerate the development of new cancer treatments.

Description

Scope of research activities

Preclinical research using primary cells from AML patients to test drug candidates:

Evaluation of the efficacy of targeted small molecules
Demonstration of mechanism of action

Conduct of studies

Steps:

Organize study set-up, technique development and quality control
Organize cytometry data management
Assist the bioinformatics engineer of the imaging and cytometry platform in analyzing the data set and interpreting results

Research infrastructure

Experimental and analysis platforms:

Preclinical research platform (hosting of preclinical cancer models; preclinical evaluation of models and therapies, phenotyping, experimental pathology)
Integrated biology platform (genomics, proteomics and metabolomics)
Imaging and cytometry platform

Models:

Primary cells from AML patients

Technical personnel:

Technician

Specifications

The platform

In vitro studies on primary cells from AML patients to evaluate and understand the mechanism of action of new molecules targeting mutations involved in the early stages of hematopoietic cell transformation.

The studies

Evaluation of anti-leukemic activity:

Morphology (cytology)
Expression of cell surface markers studied by flow cytometry and spectral cytometry to analyze the process of breaking the blockade of differentiation

Examples of partnerships

Inhibitor FHD-286 Induces Differentiation in Preclinical Models of AML - The aim of the study was to evaluate the cytotoxic activity of a pharmacological inhibitor of the BRD9 catalytic subunit (SWI/SNIF complexes) on primary samples from AML patients by various assays, including spectral cytometry analysis.

Partner: Foghorn Therapeutics

Efficacy of FT-2102 (olutasidenib) on IDH1 Acute Myeloid Leukemia - The aim of the study was to investigate by RNA sequencing the cellular/molecular pathways associated with the first steps in the lifting of the differentiation blockade induced by FT-2102 alone or in combination with 5AZAdC.

Partner: Forma Therapeutics

Study of Orally Administered AG-120 in Subjects With Advanced Hematologic Malignancies With an IDH1 Mutation - The aim of the study was to evaluate the pro-differentiation activity of AG-120 in samples from patients with AML with an IDH1 mutation (IDH1m).

Partner: Agios Pharmaceuticals