PRECLINICAL TESTING OF CAR-T CELLS FOR THE TREATMENT OF T/B ACUTE LYMPHOBLASTIC LEUKEMIA
- ATMP development
- ALL
- Gene therapy
- CAR-T cells
- Preclinical research (TRL 4-5)
Preclinical testing the efficacy of CAR-T-cell therapy in ALL, to assess the impact of CAR-T-cells on leukemia cells and lymphocyte development.
Availability of PDX models derived from patients with T/B-ALL (pediatric).
Description
Scope of research activities
Preclinical research using in vivo and in vitro models to assess the efficacy and toxicity of CAR-T-cells:
- Monitoring the development of human functional T lymphocytes in normal and pathological hematopoiesis
Conduct of studies
Humanizing mice with normal human stem/progenitor cells, monitoring normal or leukemic human hematopoietic development, testing CARTs directed against pathological cells, testing toxicity on normal cells.
Steps:
- Analysis of innovative product development strategy
- Study design
- Drafting of study plans
- Organization, implementation and conduct of studies
- Analysis and communication of results
Research infrastructure
Experimental and analysis platforms:
- Flow cytometry
- Animal experimentation (dedicated personnel)
- Animal facility
- Molecular bioengineering
- Microscopy
- Ex-vivo screening of biomolecules
Preclinical models:
- Immunodeficient mouse model of normal human hematopoiesis
- Mouse model of human leukemia
- Ex-vivo culture of T-ALL PDX (including pediatric models) and B-ALL
Specifications
The platform
Set of in vivo and in vitro tests for the evaluation of CAR-T-cells for the treatment of T/B-ALL.
The studies
Evaluation of developmental toxicity of normal T/B lymphocytes from transplantation of CD34+ cord blood cells into immunodeficient mice:
- Measurement of % and absolute number of T/B lymphocytes in thymus, spleen and bone marrow of humanized mice
Assessment of toxicity in mouse models of normal human cell xenografts:
- Measurement of % and absolute number of T/B lymphocytes in thymus, spleen and bone marrow of humanized mice
Evaluation of efficacy in PDX models of T/B-ALL:
- Measurement of human leukemic growth in humanized mice with T/B-ALL PDX
Assessment of in vitro efficacy:
- Measurement of human leukemic growth of T/B-LAL PDX in culture
Examples of partnerships
Development of new CART development conditions - The aim is to study whether the experimental conditions developed by the Smart-immune company can be used to produce effective and specific CART.
Partner : Smart Immune
Terms
OPALE entity
UMR - 1274
Head of Entity
Contact
Dr. Sandrine PalcyBusiness Development Director