Mercredi 27 Mars 2019, 11h00 : Séminaire MAbImprove

Annie Marc, Emmanuel Guedon et Isabelle Chevalot


Laboratoire Réactions et Génie des Procédés (LRGP), UMR CNRS 7274, Université de Lorraine


"Intensification et maîtrise des procédés de production de biomédicaments" 

Contact: nathalie.vourch@univ-tours.fr



La demande en forte croissance des biomédicaments produits par cellules animales impose d'intensifier les capacités de production. Ces produits incluent de nombreuses biomolécules, dont en particulier les anticorps recombinants, ainsi que des cellules utilisées elle-mêmes pour leur intérêt thérapeutique. Cependant, l'extrapolation de l'échelle de la boîte de culture à celle du bioréacteur reste loin d'être une évidence. Le défi consiste à comprendre, maîtriser et contrôler ces bioprocédés par une approche pluridisciplinaire, en vue d'obtenir des performances optimales, et ce, en dépit de l'environnement contraignant auquel sont soumises les cellules. Une vue d'ensemble des spécificités de ces procédés et des recherches en cours sera proposée et illustrée par des exemples.


Plus d’informations sur http://lrgp-nancy.cnrs.fr/spip.php?rubrique74

Vendredi 26 avril 2019, 14h, Séminaire IRCM

Akeila Bellahcène


GIGA-CANCER, Université de Liège, Belgique


"Targeting glycolysis-derived oncometabolites as a promising anti-cancer strategy”


Contact: andrei.turtoi@inserm.fr


In brief

Metabolic adaptation of cancer cells is recognized as a main hallmark of cancer. Tumour cells are notably characterized by an increased glucose uptake and a high glycolytic flux also known as the “Warburg effect”. One underestimated consequence of this glycolytic switch is the production of methylglyoxal (MG). MG is a highly reactive dicarbonyl that reacts with nucleic acids and proteins to form advanced glycation end products (AGEs), thus creating a dicarbonyl stress. The non toxic accumulation of MG and AGEs adducts are implicated in many pathological situations including diabetes, heart disease, neurodegenerative disease, ageing and cancer. Dr. Bellahcène’s team got interested since 2013 in the study of dicarbonyl stress in the development and progression of cancer. Upon MG stress, breast cancer cells show enhanced growth and metastatic potential in vivo that is efficiently reversed using carnosine, a natural MG scavenger. Given the explosion of interest and information on cancer metabolism, exploring the mechanisms regulating the levels of MG oncometabolite will be determinant for understanding tumor biology and improving cancer therapy.

Mercredi 15 mai 2019, 11h00, Séminaire MabImprove

Peter Lenting


INSERM U1176, Hémostase, Inflammation et Thrombose


"Application of classic antibodies and nanobodies in hemorrhagic disorders"


Contact: jerome.rollin@univ-tours.fr


In Brief


The treatment of hemorrhagic disorders like hemophilia and von Willebrand disease is largely dependent on replacement therapy using the missing protein. Such therapies are expensive, require frequent intravenous injections and are (in case of FVIII-replacement therapy) associated with the development of inhibitory antibodies in up to 30% of the patients. Over the last decades, alternative approaches have been or are being developed, some of which are based on the therapeutic use of antibodies or antibody-based proteins. Also in our laboratory, we have developed antibody-based therapies, some of which being advanced candidates for clinical development.

One example regards antibody LTX-508, a monoclonal antibody that binds to von Willebrand factor (VWF). VWF is a multimeric protein responsible for the recruitment of platelets. In patients that receive mechanical circulatory support (as in LVAD or ECMO), VWF is excessively degraded. Up to 50% of these patients manifest bleeding complications, which are associated with prolonged hospitalization and increased mortality. Antibody LTX-508 aims to reduce degradation of VWF under these conditions. Another example relates to a FVIII-nanobody fusion protein, designated FVIII-KB013bv. In this protein, FVIII is fused with a nanobody directed against its carrier protein VWF. The presence of the nanobody increases its affinity for VWF 25-fold, and this increased affinity is associated with a two-fold prolonged half-life and, more importantly, a 7-fold reduction in the number of mice that develop inhibitory antibodies against FVIII. Finally, we have also developed nanobodies against antithrombin, a main inhibitor of the coagulation cascade. The nanobodies interfere with antithrombin activity, and can be used to restore the hemostatic balance in hemophilia A and B. In vitro and in vivo data confirm that such nanobodies can correct for the absence of FVIII or FIX. The advantage of such nanobody-based therapy is that these antibodies can be given both subcutaneously and intravenously, while their stability may allow storage at room temperature rather than 4?C.

Lundi 20 mai 2019, 14h, salle séminaire IRCM

Ygal Haupt


MacCallum Cancer Center, Melbourne, Australia


"Novel Strategies for Restoring Tumour Suppression to Treat Cancer"


contact: laurent.lecam@inserm.fr

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