PHARMACODYNAMIC STUDIES FOR THE DEVELOPMENT OF NEW TREATMENTS FOR ACUTE MYELOID LEUKEMIA
- Preclinical development
- AML
- Targeted therapy
- Chemotherapy
- Preclinical research (TRL 4-5)
In vivo models of acute myeloblastic leukemia to validate the proof of concept of the therapeutic action of new molecules.
PDX models of different AML subtypes enable us to mimic the heterogeneity of the disease in the patient, and to study the behavior of tumor cells and their microenvironment to understand their various degrees of sensitivity to different treatments.
Description
Scope of research activities
Preclinical research using various AML-specific models to test drug candidates:
- Study of mechanism of action
- Evaluation of efficacy
- Evaluation of toxicity
Conduct of studies
Steps:
- Literature review of target and drug candidate
- Design of preliminary in vitro studies
- Design of in vivo studies
- Setting up study cohorts
- Cellular, molecular and multi-omics analysis of ex vivo samples
Research infrastructure
Experimental and analytical platforms:
- Cytometry and cell sorting
- Single-cell sequencing
- Metabolomics
- Experimental zootechnics
Models:
- Patient-derived xenograft (PDX) mouse models AML
- AML cell line xenograft mouse models
Technical personnel:
- In vivo engineer
Quality assurance
SOPF (Specific and Opportunistic Pathogen Free) sanitary status of animal experimentation area.
Specifications
The platform
A set of preclinical studies using specific in vivo models of AML.
The studies
Study of the mechanism of action of the anti-leukemic effect of drug candidates:
- Cell sorting of resistant leukemic populations
- Molecular studies of gene expression in these populations
Evaluation of anti-leukemic activity of drug candidates:
- Measurement of tumor reduction in leukemic tissues by flow cytometry
Evaluation of drug candidate toxicity:
- Terminal autopsy of treated animals to verify absence of macroscopic organ dysfunction
- Weight monitoring of animals to verify for weight loss following treatment
Examples of partnerships
Development of anti-CALCRL monoclonal antibodies - Selection and validation of a lead candidate blocking the target. Measurement of specificity, anti-leukemic efficacy and signaling in vitro and in vivo. Objective of preclinical development of lead candidate.
Partners: METATherapeutix, Biocluster MIB (Prof. Daniel Olive), Montpellier Mabs platform (GenAc)
Development of anti-CD39 monoclonal antibodies - Anti-leukemic effect in vivo by blocking the stress response after treatment.
Partners: Innate Pharma, Evitria
Development of CAR-T cells - Development of an anti-CALCRL CAR-T cell based on an anti-CALCRL monoclonal antibody developed and produced. In vitro efficacy demonstrated. Objective to demonstrate efficacy and low toxicity in vivo.
Partner: University of Geneva (Dr. Jérôme Tamburini, Dr. Federico Simonetta)
Terms
OPALE entity
CRCT (UMR-1037)
Head of Entity (METAML)
Contact
Dr. Sandrine PalcyBusiness Development Director
Other offers
PRECLINICAL MOUSE MODELS FOR NEW MOLECULES SCREENING IN THE TREATMENT OF ACUTE LYMPHOBLASTIC LEUKEMIA B
PRECLINICAL XENOGRAFT MODELS FOR THE EVALUATION OF NEW COMPOUNDS IN THE TREATMENT OF ACUTE LYMPHOBLASTIC LEUKEMIA B
DEVELOPMENT OF MOLECULAR DIAGNOSTICS KITS FOR GENOMIC ALTERATION IN LEUKEMIA AND OTHER MALIGNANT HEMOPATHIES