Engineered mesenchymal stem cells as vectors in a suicide gene therapy against preclinical murine models for solid tumors

Ikrame Amara, Elodie Pramil, Catherine Senamaud-Beaufort, Audrey Devillers, Rodney Macedo, Géraldine Lescaille, Johanne Seguin, Eric Tartour, François M. Lemoine, Philippe Beaune, Isabelle de Waziers

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Gene-directed enzyme pro-drug therapy (GDEPT) consists of expressing, in tumor cells, a suicide gene which converts a pro-drug into cytotoxic metabolites, in situ. In a previous work, we demonstrated that the combination of the suicide gene CYP2B6TM-RED (a fusion of a triple mutant of CYP2B6 with NADPH cytochrome P450 reductase) and cyclophosphamide (CPA) constituted a powerful treatment for solid tumors. In this work, we investigated the use of mesenchymal stem cells (MSCs) as cellular vehicles for the delivery of our suicide gene. MSCs were genetically engineered ex-vivo to stably express CYP2B6TM-RED. Ex vivo and in vivo investigations showed that MSCs expressing CYP2B6TM-RED were able 1) to bioactivate CPA and produce local cytotoxic metabolites in tumor sites and 2) to destroy neighboring tumor cells through a bystander effect. Intratumoral injections of CYP2B6TM-RED-MSCs and CPA completely eradicated tumors in 33% of mice without recurrence after 6 months. Rechallenge experiments demonstrated an efficient immune response. These data suggest that MSCs expressing CYP2B6TM-RED with CPA could represent a promising treatment for solid tumors to test in future clinical trials.

Original languageEnglish (US)
Pages (from-to)82-91
Number of pages10
JournalJournal of Controlled Release
StatePublished - Oct 10 2016
Externally publishedYes


  • Cyclophosphamide
  • Cytochrome P450 2B6 (CYP2B6)
  • Immune response
  • Preclinical models
  • Therapeutic stem cells

ASJC Scopus subject areas

  • Pharmaceutical Science


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