|INSERM U1183 "Cellules souches, plasticité cellulaire, médecine régénératrice et immunothérapies"||
Our research project aims to develop innovative immunotherapies for dys-immune diseases. Our work has shown that monoclonal antibodies (mAb, molecules with high therapeutic added value) are immunomodulatory agents that can determine the development of a long-term protective immune response ("vaccine effects"). On the other hand, antibodies to autologous structures 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 in HIV infection and rheumatoid arthritis are also being studied in human pathologies.
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- Naranjo-Gomez M et al. Neutrophils are essential for induction of vaccine-like effects by antiviral monoclonal antibody immunotherapies. JCI Insight. 2018 May 3;3(9). pii: 97339. doi: 10.1172/jci.insight.97339.
- Cauwels A et al. Delivering Type I Interferon to Dendritic Cells Empowers Tumor Eradication and Immune Combination Treatments. Cancer Res. 78:463-474.
- Cauwels A et al. A safe and highly efficient tumor-targeted type I interferon immunotherapy depends on the tumor microenvironment. Oncoimmunology. 2017 Nov 27;7(3):e1398876.
- Lambour J et al. Converting monoclonal antibody-based immunotherapies from passive to active: bringing immune complexes into play. Emerg Microbes and Infect Aug 17;5(8):e92. doi: 10.1038/emi.2016.97.
- Pelegrin M et al. Antiviral Monoclonal Antibodies: Can They Be More Than Simple Neutralizing Agents? Trends Micorbiol, 23(10):653-65.
- Uzé G. et al. High efficiency targeting of IFN-α activity: possible applications in fighting tumors and infections. .26. 179-182.
- Garcin G. et al. High efficiency cell−specific targeting of cytokine activity. Nature Commun. 5:3016 doi: 10.1038/ncomms4016.
- Sistigu A. et al. Cancer cell-autonomous contribution of Type 1 interferon signaling to the efficacy of chemotherapy. Nature Medecine. 11. 1301-1309.
- Tomasello E. et al. Harnessing mechanistic knowledge on beneficial versus deleterious IFN-I effects to design innovative immunotherapies targeting cytokine activity to specific cell types. Frontiers in Immunology. 5. 526.
- Nasser R. et al. Control of regulatory T cells is necessary for vaccine-like effects of antiviral immunotherapy by monoclonal antibodies. Blood 14;121(7):1102-11.
- Michaud HA. et al. A crucial role for infected-cell/antibody immune complexes in the enhancement of endogenous antiviral immunity by short passive immunotherapy. PLoS Pathog. Jun 10;6(6):e1000948.
- Nasser R. et al. Long-lasting protective antiviral immunity induced by passive immunotherapies requires both neutralizing and effector functions of the administered monoclonal antibody. J. Virol. 84: 10169-81.
- Gros L, et al.. (2008) Endogenous cytotoxic T-cell response contributes to the long-term anti-retroviral protection induced by a short period of antibody-based immunotherapy of neonatally infected mice. J Virol., 82: 1339-1349.
- Gros L. et al. Induction of long-term antiviral endogenous immune response by short monoclonal antibody treatment. J Virol, 79, 6272-6280.
- Dreja H. et al. The 667 monoclonal antibody recognizes the VRA motif of the ecotropic CasBrE retrovirus envelope glycoprotein and exerts its neutralizing activity through direct inhibition of the binding to the viral receptor. J Virol, 77: 10984-93.
- Pelegrin M. et al. (2000) Immunotherapy of a viral disease by in vivo production of therapeutic monoclonal antibodies. Hum. Gene Ther, 11, 1407-1415.
More references, click on PubMed:
tel: +33 4 67 33 04 59
adress: INSERM U1183, CHU Saint Eloi, IRMB, 80 Avenue Augustin Fliche, 34295 Montpellier cedex 5, France
PELEGRIN Mireia (CRCN CNRS)
UZE Gilles (DR1 CNRS)*
NARANJO-GOMEZ Mar (CRCN INSERM)
MARSILE Soledad (doctorante, Université de Montpellier)
RISSEL Florian (Médecin CHU Montpellier, formation en Master 2, Université de Montpellier)
DESPRES Justine (Master 2, Université Paris-Sud)
GARCIN Geneviève (CDD)*
OGOR Thomas (doctorant, Université de Montpellier)*
* will join IRMB in 2020
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