Michel Sadelain, MD, PhD

The advent of technologies that permit efficient gene transfer in human primary cells creates novel therapeutic perspectives. Based on the use of recombinant oncoretroviruses and lentiviruses, we are investigating how to control transgene expression in vivo in hematopoietic stem cells and how to augment immune responses against tumor cells.

Our current studies on the first topic focus on the role of locus control regions and insulators in regulating the transcription of randomly integrated beta globin transgenes.

With respect to tumor immunity, we are exploring different strategies to target T cells to tumor cells, either by facilitating dendritic cell-T cell interactions or by enhancing the co-stimulation of T cells that engage tumor cells.

Isabelle Riviere, PhD, is the Co-Director of the Gene Transfer and Somatic Cell Engineering Facility. The facility is responsible for the production of clinical grade retroviral vectors and plasmid DNA for gene therapy clinical trials. The transduction facility focuses on the genetic engineering of hematopoietic stem cells, dendritic cells, and T lymphocytes.

We are also using gene transfer technology in order to investigate the molecular pathways that influence the differentiation of naïve T lymphocytes toward the Th1 or Th2 phenotype. This may play a crucial role in the outcome of immune responses against foreign or self antigens, including those expressed in tumor cells.