ANTIBODIES AND IMMUNOMODULATION
Phone: +33 4 67 33 52 67
The group members:
PELEGRIN Mireia (DR2 / CNRS)
UZE Gilles (DR1 / CNRS)
NARANJO-GOMEZ Mar (CRCN / INSERM)
MARSILE Soledad (PhD-Student)
OGOR Thomas (PhD-Student)
ABBA-MOUSSA MOUSTAPHA Daouda (IR, CDD)
SOUCHARD Manon (IE, CDD)
BRU Rémi (Master 2)
Innate and adaptive immunity
Characterization of innate and adaptive immune responses in humans and mice
Structure-function relationship of antibodies
Interferon systems in humans and mice: from ligands to signaling
Experimental models of viral infections and cancer
Our research project aims to develop innovative immunotherapies for dys-immune diseases. Our work has shown that monoclonal antibodies (mAb, molecules with high therapeutic value) are immunomodulatory agents that can determine the development of a long-term protective immune response (“vaccine effects”). On the other hand, antibodies against autologous structures (auto-antibodies) can develop and cause different forms of tissue damage causing autoimmune diseases. It is now clear that the impact of antibodies (therapeutic mAb or auto-antibodies) on the induction of the immune response involve different mechanisms among which type I interferons (IFN-I) are key actors. A major challenge is therefore to identify these mechanisms (common or specific) involved in the induction of the antibody-mediated immune response. This would enable us to control them in order to promote them in the context of immunotherapies for infectious or cancerous diseases or, on the other hand, to slow them down in the context of autoimmune diseases by developing innovative immunotherapies. Thus, using in vitro and in vivo approaches, our work aims to study the role of mAbs/autoantibodies in the recruitment and activation of immune system cells. Different mouse models of pathologies (viral infections, cancerous pathologies and rheumatoid arthritis) are being studied and innovative tools are being developed that allow the targeting of IFN agonists and antagonists in a specific cell type. Antibody-mediated immunomodulation mechanisms are also being studied in human pathologies such as HIV-1 and SARS-CoV2 infection as well as in rheumatoid arthritis.
1- Identification and conceptualization of mechanisms involved in the induction of vaccinal effects by antiviral antibodies.
2- Identification of a key immunomodulatory role of neutrophils in the induction of protective antiviral immunity.
3- Identification of an immunomodulatory role of NK cells during antiviral therapy
4- Development of innovative tools that allow the targeting of IFN agonists and antagonists in a specific cell type.
Our team is a member of the European Consortium “ACT4COVID” which is developing a multi-center research project for a better understanding of how the immune system react in response to SARS-CoV-2 infection, and for the development of new treatments to be proposed according to the host’s cellular response to COVID-191. The project, which is supported by a 5 million euros investment through an agreement with the company Cellnex, aims to detect and obtain T cells that fight SARS-CoV-2 infection.
The project aims to identify different immunological profiles associated with different clinical prognosis in patients with COVID-19. This will allow the detection of biomarkers capable of predicting the evolution of patients. In parallel, the consortium aims to develop cellular immunotherapies for the different phases of the infection. On the one hand, natural T cells from samples of patients who have passed COVID-19 will be used to stop the infection. On the other hand, specific anti-SARS-CoV-2 CAR-T cells are being developed. For this purpose, the patient’s T cells will be modified to fight against viral infection. In parallel, innovative cell-therapy approaches will be developed to control the hyper-response through natural or post-manipulation regulatory T cells.
This project should allow to finely dissect the cellular immune responses to SARS-CoV-2 infection in order to develop new diagnostic tools and therapeutic approaches based on cell therapy. The knowledge gathered by the consortium could be exploited to fight other viral diseases.
The consortium is composed of six leading immunotherapy research teams in Europe:
- Hospital Clínic de Barcelona-IDIBAPS, Barcelona, Espagne, (Coordinator: Dr. Manel Juan-Otero)
- the Blood and Tissue Bank (BST) of Barcelona, Espagne
- the Gregorio Marañón University Hospital of Madrid, Espagne
- the Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) of Meldola, Italie
- the IRCCS of the San Raffaele Hospital (HSR) of Milan, Italie
- the Institute for Regenerative Medicine and Biotherapy/Inserm-U1183 associated with the University Hospital of Montpellier, France
Our team is actively involved in this project thanks to our expertise in the field of antiviral immunotherapies and to the close collaboration with different teams from Montpellier: Dr. Pierre Martineau (IRCM/GenAc, Montpellier), Dr. Christine Chable-Bessia (CEMIPAI, Montpellier) and Dr. Delphine Muriaux (CEMIPAI/IRIM, Montpellier).
1 A consortium of European hospitals led by Clínic IDIBAPS is launching a cellular immunotherapy project to tackle COVID-19 with the support of Cellnex Telecom. 2020.