CV Science

Christophe FERRAND PhD Molecular Biology

Course and current status

•  1990: Master II (DEA) degree in Biology and Cellular and Molecular Biochemistry

University of Franche-Comté, Faculty of Medicine and Pharmacy, Besançon, France. Morpho-functional Histology UA CNRS 0561 research team "Cloning and sequencing of mRNA encoding a hypothalamic peptide immuno-reactive to certain anti-prolactin immune sera”. (MRT research grant) 

• 1994: PhD Thesis, Health and Life Sciences

University of Franche-Comté, Faculty of Medicine and Pharmacy, Besançon, France. Morpho-functional Histology UA CNRS 0561 research team “Contribution to the identification in lateral hypothalamus neurons of rats of a neuropeptide using anti-prolactin immune sera”.Supervisor: Pr D Fellmann

Since 1 January 1997 : Researcher, Immuno-Molecular Therapies in Cancer research group, EFSB/F-C, Besançon, France (in charge of the molecular biology activities, student supervision, teaching, member of the European working group Biomed-1 on “suicide gene” TK gene therapy).

• 2004 : Habilitation à Diriger les Recherches (HDR) (Research Habilitation Degree)

University of Franche-Comté, Faculty of Medicine and Pharmacy, Besançon, France. INSERM U645 / IFR133 / EA 2284 research team

• 2004-now : PI at UMR1098 (ex645) INSERM, EFS/BF-C, SFR133, Besançon France - Head of molecular onco-hamatology lab

Scientific summary

Our team is involved on host-graft-tumor interactions and corresponds ("Thérapeutique Immuno-Moléculaire & Cancer", “Immunomolecular Therapies in Cancer”, TIM-C, directed by Prof. C Borg). Based on our previous works (in vitro study & clinical trial) concerning a suicide gene therapy approach to control Graft vs Host Disease (GvHD) allowing us to acquire a great experience on T-cells (Blood 2001a, Blood 2007, Mol Immunol 2008), we are currently developing anti-tumor immunotherapy approaches using reprogrammed TCR (gTCR) or Chimeric antigen Receptor (CAR). We proposed two approaches: suicide gene therapy to control alloreactive T cells and alloreactive NK cell administration. NK cells constitute an interesting candidate for immunotherapy since molecules involved in tumorigenesis or cancer progression (such as bcr-abl, for instance) may participate to NK activation (Blood 2008).

Expertise acquired from HS-tk gene splicing analysis (Blood 2001b) was transposed to the CD20 gene. CD20 is expressed by several B cell malignancies and is the target of Rituximab. Genetic introduction of CD20 is also proposed to be used as a suicide gene to prevent GvHD, since it combines both GMC selection by immunomagnetic cell sorting and GMC in vivo elimination by Rituximab treatment. While studying the combined potential “suicide” and “selection” properties of the CD20 molecule, we identified a new in-frame alternative splicing of CD20 gene messenger leading to a truncated protein –called ΔCD20-, preventing its expression at membrane level and leading to Rituximab resistance (Blood 2010). In this setting, we tried to characterize normal circulating CD20⁺ T cells previously described by others. To overcome the resistance to Rituximab due to the ΔCD20 protein, we propose to develop cytotoxic T lymphocytes (CTL) directed against the alternatively spliced CD20-derived epitopes. This novel therapeutic approach will constitute a more integrated project with the characterization of new antigens to target for cancer immunotherapy following by the selection of most effective TCR, the cloning of these TCR and their transfer into EBV-specific T cell lines.