Immunoregulation and Biotherapy (I-BIOT)

Contacts

Direction de l'équipe
José Cohen Head José Cohen

Tél.: 01 49 81 44 75
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Topic

 

Our team works on the modulation of the immune response applied to allografts (including gestation) and cancer. Our conceptual contributions rely on original discoveries in the field of checkpoints of the immune response (IL4I1, TNFR2, TFH interaction – B cells). We also take a fresh look at the interactions between immune response and tumor microenvironment by studying the interdependencies between tumor vascular normalization and quality of the immune response with or without therapeutic intervention.

 

We have several experimental models in the field of grafts (skin, HSC) in immunocompetent or immunodeficient mice. We have strong expertise in surgery, anatomopathology, immunohistochemistry, flow cytometry, 3D imaging (in collaboration with the Vision Institute), ultrasound of small animals and on tumor analysis (human or mouse) in close collaboration with locally-pathology and oncology departments (digital pathology, patient monitoring).

 

We are also developing tumor organoids from cell lines or directly from patient biopsies, in order to limit animal testing while expanding our field of investigation.

 

Our interactions are close with nephrology, clinical hematology, medical oncology, radiotherapy and obstetrics gynecology departments and we host a large part of their translational research activities.

 

We lead the clinical investigation center in biotherapy (J Cohen/P Grimbert), which we use as a platform for the development of early phase clinical trials based on our research. We also coordinate the “Fédération hospital-universitaire” FHU “TRUE, Innovative therapy for immune disorders” (PI Philippe Grimbert) and the “Focis center of excellence” in transplantation and cancer (PI José Cohen).

 

Our team also hosts Biopredic International, (Ismael Ben Mosbah, Manager and Fatiha Mahtout, Laboratory technician). Biopredic’s expertise relates to the isolation, production and distribution of human and animal biologics, including tissues, primary cells, cell lines and reagents.

 

Expected benefits and Valuation

 

Our goal is to develop new therapeutic tools based on an in-depth knowledge in the fields of transplantation and cancer, two target fields of pathologies of dysfunctions of the immune response. Our recent work has led to several invention patents, some of which are licensed. We have also many interactions with private companies through the development of clinical trials or new biotherapy tool development.

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Selected publications

Cossutta M, Darche M, Carpentier G, Houppe C, Ponzo M, Raineri F, Vallée B, Gilles ME, Villain D, Picard E, Casari C, Denis C, Paques M, Courty J, Cascone I. Weibel-Palade Bodies Orchestrate Pericytes During Angiogenesis.

Arterioscler Thromb Vasc Biol. 2019 Sep;39(9):1843-1858.

Kwun J, Matignon M, Manook M, Guendouz S, Audard V, Kheav D, Poullot E, Gautreau C, Ezekian B, Bodez D, Damy T, Faivre L, Menouch D, Yoon J, Park J, Belhadj K, Chen D, Bilewski AM, Yi JS, Collins B, Stegall M, Farris AB, Knechtle S, Grimbert P. Daratumumab in Sensitized Kidney Transplantation: Potentials and Limitations of Experimental and Clinical Use.

J Am Soc Nephrol. 2019 Jul;30(7):1206-1219.

Leibler C, Thiolat A, Hénique C, Samson C, Pilon C, Tamagne M, Pirenne F, Vingert B, Cohen JL, Grimbert P. Control of Humoral Response in Renal Transplantation by Belatacept Depends on a Direct Effect on B Cells and Impaired T Follicular Helper-B Cell Crosstalk.

J Am Soc Nephrol. 2018 Mar;29(3):1049-1062.

Aubatin A, Sako N, Decrouy X, Donnadieu E, Molinier-Frenkel V, Castellano F. IL4-induced gene 1 is secreted at the immune synapse and modulates TCR activation independently of its enzymatic activity.

Eur J Immunol. 2018 Jan;48(1):106-119.

Molinier-Frenkel V, Prévost-Blondel A and Castellano F. The IL4I1 enzyme: a new player in the immunosuppressive tumor microenvironment.

Cells. 2019 Jul 20;8(7)

Maury S, Chevret S, Thomas X, Heim D, Leguay T, Huguet F, Chevallier P, Hunault M, Boissel N, Escoffre-Barbe M, Hess U, Vey N, Pignon JM, Braun T, Marolleau JP, Cahn JY, Chalandon Y, Lhéritier V, Beldjord K, Béné MC, Ifrah N, Dombret H; for GRAALL. Rituximab in B-Lineage Adult Acute Lymphoblastic Leukemia.

N Engl J Med. 2016 Sep 15;375(11):1044-53. doi: 10.1056/NEJMoa1605085.

Leclerc M, Naserian S, Pilon C, Thiolat A, Martin GH, Pouchy C, Dominique C, Belkacemi Y, Charlotte F, Maury S, Salomon BL, Cohen JL. Control of GVHD by regulatory T cells depends on TNF produced by T cells and TNFR2 expressed by regulatory T cells.

Blood. 2016 Sep 22;128(12):1651-9.

Gilles ME, Maione F, Cossutta M, Carpentier G, Caruana L, Di Maria S, Houppe C, Destouches D, Shchors K, Prochasson C, Mongelard F, Lamba S, Bardelli A, Bouvet P, Couvelard A, Courty J, Giraudo E, Cascone I. Nucleolin Targeting Impairs the Progression of Pancreatic Cancer and Promotes the Normalization of Tumor Vasculature.

Cancer Res. 2016 Dec 15;76(24):7181-7193.