Sensibilisation de cellules tumorales au cyclophosphamide par transfert de gène : de l'in vitro à l'in vivo

Abstract : Anticancer therapies had, in recent years, an important development that results in an improvement in the quality of life of patients. However, the occurrence of resistance and the significant proportion of untreated cancer force us to consider the development of new anticancer strategies. We have developed a new technique based on the principle of suicide gene using the gene of cytochrome P450 2B6 associated with cyclophosphamide (CPA). This technique involves the transfer of a gene metabolizing an anticancer prodrug within the tumor allowing tumors sensitization to this prodrug. The first objective of this work was to improve the metabolism of the prodrug in building a mutated CYP2B6 fused with the reductase gene essential partner of CYP. In a second step we transferred the CYP2B6TM-RED gene in tumor cells that have been significantly sensitized. These results were confirmed on in vivo models of immunocompetent mice. In addition to the cytotoxic effect, mice were able to develop a specific anti-tumor immunity. This suggests to us that this method can protect against recurrence and metastasis. The good results obtained in the development of this new anticancer strategy, let us hope for a future transition into clinic. For this, new animal models will be developed to definitively validate the method.
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Walid Touati. Sensibilisation de cellules tumorales au cyclophosphamide par transfert de gène : de l'in vitro à l'in vivo. Sciences agricoles. Université René Descartes - Paris V, 2013. Français. ⟨NNT : 2013PA05P618⟩. ⟨tel-00952150⟩

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