Dominique CATHELIN

En résumé

Entreprises

• Inovarion - Chef de Projet R&D Sciences de la Vie

  PARIS 13 2016 - maintenant

• INSERM UMR_S1155- Hopital Tenon, Paris 20ième - Chercheur post-doctorat

  2011 - 2016

• CCIT centre for cancer immune therapy, University Hospital Herlev, Copenhagen Denmark - Chercheur post doc

  2009 - 2011 Project: Reengineering clinical-grade dendritic cells to develop a highly potent vaccine for breast cancer therapy
  In order to increase the immune efficiency of Ag loaded-DC vaccines, it seems important to counterbalance the immune tolerance induced by tumor cells in the tumor environment to lead to a complete antitumor immune response in patients. Indeed, DCs express a large variety of immunosuppressive proteins that negatively influence T cell-mediated immunity, which leads to inadequate immune responses to tumors. So, it seems essential to exactly know the expression status of these immunosuppressive proteins in DCs and to modulate the DCs maturation process to lead to an appropriate T cell response. In this way, we screened several well-known and characterized immunosuppressive molecules in DCs which are differentiated in the lab and already used in clinical trials to improve the efficacy of the tumor vaccines. I focus my works on the interleukin-10 and the use of RNA interference (RNAi) as a mean of selectively silencing genes encoding this immunosuppressive molecule in DCs.

• INSERM U866 - Doctorant

  2004 - 2008 The subject of my project was the use of cell fusion in antitumor immunotherapy. I specifically studied the death mechanism of fused tumor cells induced by the expression of a viral fusogenic membrane protein in a murine melanoma model. Thus, I highlighted a protective effect of the injections of syncitia resulting from the fusion of tumor cells. Indeed, this immunotherapy leads to the protection of about 70% of the animals against new injections of cancer cells. I also collaborated with Dr Larmonier (Tucson, Texas). The results of the immunogenic effects of death induced by fusion on rat dendritic cells were published in 2006 (Larmonier et al., Apoptosis, 2006).
  In parallel, I highlighted a new property of the dendritic cells: their cytotoxic effect on tumor cells. We have shown that rat bone marrow derived dendritic cells (BMDC) are able to exert a cytotoxic activity on several tumor cell lines. This cytotoxicity is increased in presence of LPS and is mediated by nitric oxyde (NO) release. The tumor cell death mechanism induced by these LPS activated BMDC is not an apoptosis but seems to be necrotic. Moreover, these BMDC exhibit a mature phenotype, keep their capacity to endocyte antigens and are able to induce the proliferation of allogeneic T lymphocytes. In vivo, LPS intratumoral injection leads to an arrest of the tumor growth associated with an overexpression of the inducible NO synthase in intratumoral dendritic cells (Cathelin et al., Journal of Immunology, 2007).
  In addition, I collaborated in studies focused on CD4+CD25+ regulatory T cells (Treg). First of all, I participated in the first identification of this immunosuppressive population in rats. In this work we demonstrated that the number on these cells increases during the tumor growth in a rat colorectal tumor model. We have also shown that a combination of chemotherapy (cyclophosphamid) and immunotherapy (BCG) eradicates this immunosuppressive T cells and leads to the cure of established tumors in vivo (Ghiringhelli et al., European Journal of Immunology, 2004). This work was the base of a clinical trial in which I was involved. In this study, we demonstrated that cancer patients have an important level of Treg in comparison of healthy people. However, a single intravenous infusion of cyclophosphamid in association with a non-specific immunotherapy by intratumoral bacillus Calmette-Guérin (BCG) failed to modulate significantly Treg numbers or function (Audia et al., Clinical and Experimental Immunology, 2007).

Formations

• Université Dijon Bourgogne (Dijon)

  Dijon 1999 - 2008 Biochimie Immunologie
  
  Thèse

• Lycée René Cassin

  Macon 1996 - 1999 S SVT

Réseau

• Alexandrine FRAICHARD

• Amandine MARTIN

• Antoine BONNEFOY

• Delphine MERINO

• Guillaume BOITEUX

• Jérôme FLATOT

• Jessy CARTIER

• Karine COTTRINO

• Myriam LAMRANI

• Rodolphe FILOMENKO