Immunotherapy in Transplantation And Autoimmunity

Team leaders

Team 3
Alumni

Description

Our team established a Public-Private Partnership (PPP) where physicians and scientists from the public (INSERM-CNRS-CHU) and private sectors (OSE Immunotherapeutics) are interacting to promote the development of novel therapeutic strategies emerging in our group, from pre-clinical concepts to clinical development.

Such research projects are made possible thanks to 3 technological platforms led by our team:

  • LGA (Large Animal Facility; Biogenouest label) where kidney transplantations in pigs and primates are performed
  • Humanized rodents’ platform (incorporated in the Labex IGO)
  • Recombinant proteins and antibodies production platform (to produce several grams/year, enough to conduct research in primates).

Our team aims at setting up some novel therapeutic strategies to control immune responses and install immune tolerance

We have developed the first selective CD28 antagonists (FR104) which is now part of an industrial partnership with Janssen Biotech Inc. for its clinical development in rheumatoid arthritis and in transplantation (kidney and bone marrow). We will carry out ancillary studies to assess regulatory mechanisms in the different phase II trials.

The role of SIRP-alpha/CD47 axis is under investigation in the control of the suppressive activity of myeloïd-derived suppressor cells with novel SIRP-alpha antagonists in autoimmunity, tumor immunology models, and in tumor xenograft models in humanized rodents. 

In collaboration with team 4, our team is also driving the evaluation, in our kidney transplantation primate model, of novel CD127 antagonists that might selectively impact effector T cells and promote regulatory cells, therefore inducing transplant tolerance. Impact of CD127 antagonists on ulcerative colitis is also looked at in a novel IBD model in humanized mice. 

Vascular injuries is another thematic of our team, with two approaches:

  • Induction of endothelial accommodation of transplanted kidneys, using a perfusion system with anti-HLA antibodies.
  • Cross-talk between inflammatory cells and endothelial cells are deciphered in the context of vascular insult and vascular accommodation (antibodies mediated) respectively in autoimmunity and transplantation. Focus is given to microRNAs’ expression profiles and to their transfer from inflammatory cells to endothelial cells as well as transcriptional and molecular responses of endothelial cells.