Ph.D. Thesis in Bioproduction (M/F)

Job Description

Thesis Subject

-This thesis project is part of the PEPR Biotherapies and Bioproductions “Mono-Chem” project, which aims to produce genetically modified human monocytes capable of overcoming antigenic escape, as well as to exploit the intrinsic biological properties of monocytes (Mo) to achieve therapeutic efficacy against triple-negative breast cancer (TNBC) tumors. Improving the biofunctionality of Mo cells makes it possible to transform them into therapeutic vectors that naturally migrate to tumors. While the production of the newly functionalized cells will be optimized by the partners on a so-called laboratory scale, the candidate will need to establish robust processes that comply with GMP (Good Manufacturing Practices) for clinical translation.To this end, the doctoral student will develop a scientific and technological methodology to simultaneously optimize the processes for the isolation and transduction of monocytes (Mo) under GMP conditions, while ensuring that the biopharmaceuticals produced meet the required standards. Optimization of the Mo isolation process under GMP conditions. Peripheral blood mononuclear cells (PBMCs) will be isolated from leukocyte-platelet layers (provided by EFS Grand Est) using the Sepax C-Pro closed-system. Subsequently, various isolation methods will be compared on the CliniMACS Prodigy automated system. Monocytes will be isolated either by an immunomagnetic depletion method (CD3/CD19/CD56 depletion) or by a CD14+ enrichment method. The method to be used will be selected based on purity, yield, viability, and the state of cellular activation after selection. Optimization of the Mo transduction process under GMP conditions. Two methods will then be compared for the transduction step using the selected lentiviral vectors: either the CentriCult chamber with the appropriate transduction program on the CliniMACS Prodigy automated system, or the G-Rex bioreactor under agitation conditions. The G-Rex offers greater flexibility, if necessary, in terms of culture volume and agitation speed to increase the transduction rate. The expected specifications for the advanced therapy medicinal product (ATMP) are: greater than 80% CD14+ cells, greater than 80% viability, and greater than 50% modified monocytes. In addition, monocytes and macrophages will be characterized using validated functional assays adapted from those developed by a project partner.

Your Work Environment

The thesis work will take place at the MTInov Biotherapies and Bioproductions integration center, based in Vandoeuvre-lès-Nancy. This integration center is supported by the Cell Therapy and Tissue Bank Unit at the Nancy University Hospital (CHRU) and the Reactions and Process Engineering Laboratory (UMR CNRS 7274) in Nancy. This platform enables the study, optimization, and scaling up of cellular biopharmaceuticals, thanks to its expertise in cell culture in stirred bioreactors (monitoring, intensification, modeling, design) as well as scale-up to clinical-grade production in accordance with Good Manufacturing Practices (GMP). The collaboration between the UTCT and LRGP teams has resulted in a multidisciplinary partnership with complementary activities focused on biotherapies, bioproduction, and the development of bioprocesses to improve the yields and quality of cellular and cell-based products.

Constraints and risks

Operations will be carried out in a controlled production area.

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

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