PLATFORM FOR DEVELOPING AND IMPLEMENTING TESTS FOR PRECLINICAL VALIDATION IN VITRO, EX VIVO, AND IN VIVO (ACUTE LEUKEMIA)

Preclinical development

Toutes thérapies

Preclinical research (TRL 4-5)

TrGET is a preclinical testing platform specializing in the implementation and development of in vitro and in vivo tests to assess the involvement of a target gene in tumorigenesis or the biological activity of innovative single or combined therapeutic solutions.

The platform is the result of significant technological development (development of tests, tools and cellular and animal models proposed). It offers a variety of flexible and adaptable tests, based mainly but not exclusively on bioluminescence technology. Models are developed in close collaboration with the hematology department and the early-phase clinical investigation center of the Institut Paoli-Calmettes (cancer comprehensive center - CLCC).

Description

Scope of research activities

Preclinical research using in vivo and in vitro models to discover new therapeutic avenues:

Target validation
Evaluation of drug candidates
Evaluation of combination effects

Conduct of studies

Steps :

Study design in co-construction with the partner
Definition of means/resources and proposed schedule (steps, GO/NO-GO, etc)
Carrying out of the experimentation in constant contact with the partner (with any necessary adjustments)
Data analysis and study report with recommendations

Organization

Dr. Yves Collette, Scientific Director
Dr. Rémy Castellano, Operational Manager

Research infrastructure

Experimental and analysis platforms:

Access to ECHO550 (nL) high-throughput acoustic distribution system integrated into ACCESS robotic station (Beckman Coulter) and Pherastar reading system (BMG Labtech)
RS2000 X-ray generator (RadSource)
Small animal imaging system (Optima Photon Imager, BioSpace Lab) equipped with X-ray module, MiniHub gas anesthesia station (TEM-SEGA)
L2 cell culture laboratory
SOPF animal facility

Models :

CDX acute leukemia models (>20 including bioluminescence)
PDX acute leukemia models (>30)
Cell lines derived from murine AML tumors
Xenobank annotated and characterized (in vivo and ex vivo)
Primary sample collection (acute leukemia)

Technical staff :

1 scientific manager and 1 operational engineer manager
2 engineers and 2 highly qualified technicians
2 engineers

Quality assurance

Level 3 Quality approach (GIS IBiSA standards)
IBiSA certification
Aix Marseille University Technology Platform certification

Specifications

The platform

A set of technologies for the development of specialized in vitro and in vivo tests, for the validation of therapeutic targets or drug candidates for the treatment of acute leukemia.

The studies

In vitro tests:

Multiplex tests (96/384-well format): proliferation/cytotoxicity; cell death pathways (apoptosis, ferroptosis, necroptosis, etc.); clonogenicity; migration
-Sensitivity/resistance profiles to drug collections (possible design)
Evaluation of combination effects (synergy, additivity, antagonism)

In vivo tests:

Graft uptake (syngeneic models, immunocompromised mice, orthotopic, etc)
Monitoring by flow cytometry and/or non-invasive intravital imaging in small animals: measurements (number of leukemia cells/µL blood, photons); progression or doubling time / dissemination (blood, marrow, spleen, etc.) / survival, etc
Limit dilution (LSC)
Modalities and timing of therapeutic solution administration, efficacy, combination

Examples of partnerships

Preclinical evaluation of BTN3A antibodies in combination with LTgd in AML xenograft models – Contract studies to develop a proof-of-concept model and evaluate the activity of antibodies targeting a new innate immune checkpoint in preclinical models of AML. This programme has also resulted in a publication co-authored with the partners (De Gassart A et al, Science Translational Medicine 2021, PMID: 34669444) and is part of an early phase trial involving the Institut Paoli-Calmettes (clinicaltrials.gov : NCT04243499).

Partner: Imcheck Therapeutics

DIAC2010 preclinical evaluation in AML – Contract studies to evaluate the preclinical anti-leukemic efficacy of a selective KIF20A inhibitor: DIAC2010. In this study, we have characterized anti-tumoral activity against acute myeloid leukemia models (AML), both in vitro (cytotoxic activity, cell cycle blockade, apoptosis induction) and in vivo, in mice models (both in bioluminescent CDX and PDX-models). This programme has also resulted in publications co-authored with the partners (Blood, ASH 2022 abstract DOI: 10.1182/BLOOD-2022-166820. And Cancer Research, AACR 2017, abstract DOI: 10.1158/1538-7445.AM2017-4140).

Partner: Diaccurate

Terms

OPALE entity

CRCM / IPC (UMR-1068)

Contact

Other offers

CLINICAL INVESTIGATION CENTER FOR THE SPONSORING AND CONDUCT OF PHASE I TO III INTERVENTIONAL CLINICAL TRIALS (ALL/AML/MPS/MDS)

CLINICAL INVESTIGATION CENTER FOR THE COORDINATION AND CONDUCT OF PHASE I TO III CLINICAL TRIALS IN LEUKEMIA AND RELATED DISEASES (AML, MPS, MDS, ALL)

PLATFORM FOR ACCELERATING THE DISCOVERY AND OPTIMIZATION OF NEW BIOACTIVE MOLECULES (ACUTE LEUKEMIA)