PRECLINICAL XENOGRAFT MODELS FOR THE EVALUATION OF NEW COMPOUNDS IN THE TREATMENT OF ACUTE LYMPHOBLASTIC LEUKEMIA B
- Preclinical development
- ALL
- Targeted therapy
- Chemotherapy
- Preclinical research (TRL 4-5)
Utilization of preclinical models using human B-ALL xenografts.
The originality and competitive advantages of this offer are based on:
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- Privileged access to the Toulouse Cancer University Institute's biological resource center (CRB-IUC), and in particular to the HIMIP tumor library (Inserm Hematological Malignancies in the Midi-Pyrénées region), bringing together collections of frozen biological samples (blood, bone marrow) and associated information (clinical data)
- Access to samples of ALL-B cells from patients at diagnosis and relapse
- Generation of patient-derived xenograft (PDX) models of ALL-B from patients leukemia cells at diagnosis and relapse
- Stocking of frozen cells from PDXs transplantable into NOD-SCIDgc-/- immunodeficient mice for expansion of patient leukemia cells in vivo
- Evaluation of the kinetics of in vivo leukemic reconstitution by bone marrow puncture in live animals
- Evaluation of drug candidate efficacy in vivo by bone marrow puncture on live animals
Description
Scope of research activities
Preclinical research using a PDXs model for the evaluation of drug candidates on human ALL-B leukemia cells.
- Transplantation of human ALL-B cells (from diagnosis and/or relapse) into NOD-SCIDgc-/- (NSG) immunodeficient mic
- Kinetics of leukemic reconstitution in live animals
- In vivo treatment by intraperitoneal, intravenous or osmotic pump routes
- Evaluation of the efficacy of the drug candidate on leukemic development
Conducting studies
Steps:
- Analysis/definition of study strategy
- Clinico-biological characterization (oncogenic subtype, secondary mutations, phenotypic classification) of the cells of the patient(s) with whom the study will be conducted
- Purchase of primary cell ampoules stored in DMSO and available at the HIMIP CRB
- Transplantation, expansion and follow-up of engraftment of patient cells into NSG immunodeficient mice
- Testing the molecule on the in vivo development of leukemia cells in xenografts
- Molecule testing in mouse models of ALL-B (read more)
- Analysis and communication of results.
Research infrastructure
Experimental and analysis platforms:
- Animal facility
- Cell sorting platform
- Analysis cytometer
Models:
- Human ALL-B and NSG immunodeficient mice
Technical personnel:
- Design engineer for screening and analysis
Specifications
The platform
A set of preclinical in vivo models of human B-ALL for the evaluation of drug candidates.
The studies
- Thawing of patient or PDX samples and transplantation into NSG immunodeficient mice
- Kinetics of human ALL-B development (% hCD45+hCD19+) will be analyzed by regular bone marrow aspiration
- Transplanted mice will be treated (n=5) or not (Vehicle, n=5) with the drug candidate intraperitoneally, intravenously or with osmotic pumps (Alzet Model 2001, 1 mL/h) implanted in the animal for one week
- The efficacy of the treatment on leukemic development will be assessed by the presence of human blasts in the peripheral blood, BM and spleen of the mice (percentage and absolute number)
- The effects of the drug candidate on the propagation and self-renewal of human leukemia cells can be assessed by serial transplantation followed by survival curves for the mice
Terms
OPALE entity
CRCT (UMR-1037)
IGAALD team
Contact
Dr. Sandrine PalcyBusiness Development Director
Other offers
PHARMACODYNAMIC STUDIES FOR THE DEVELOPMENT OF NEW TREATMENTS FOR ACUTE MYELOID LEUKEMIA
PRECLINICAL MOUSE MODELS FOR NEW MOLECULES SCREENING IN THE TREATMENT OF ACUTE LYMPHOBLASTIC LEUKEMIA B
DEVELOPMENT OF MOLECULAR DIAGNOSTICS KITS FOR GENOMIC ALTERATION IN LEUKEMIA AND OTHER MALIGNANT HEMOPATHIES