Development of new therapeutic antibodies formats directed against the folate receptor alpha.

Abstract

Event Abstract Back to Event Development of new therapeutic antibodies formats directed against the folate receptor alpha. Davide Bernareggi1, Elena Luison1, Alessandro Satta1, Barbara Frigerio1, Silvana Canevari1 and Mariangela Figini1* 1 Fondazione IRCCS - Istituto Nazionale dei Tumori, Italy In our laboratory two monoclonal antibodies (Abs) directed against the folate receptor alpha (FRα), MOv18 and MOv19 were discovered, providing the foundation upon which to build new human Abs. Using phage display technology were developed fully human Fab fragments with the same specificity of the murine Ab MOv19 and two of them, AFRA4 and AFRA5.3 were later engrafted in complete immunoglobulins. These new reagents were assessed for binding properties and specificity on FRα and epithelial ovarian cancer cell lines. AFRA complete antibodies of IgG1 and IgE isotype were compared with ChiMOv19 for their binding properties and the IgG1 for the ability to enhance the effectors functions, as evaluated by antibody dependent cell-mediated cytotoxicity (ADCC) assays. Enhancement of ADCC on high FRα expressing cells, comparable to that of ChiMOv19, was observed for AFRA Abs despite their reduced binding affinity and different binding kinetics. The complete human structure could be probably more efficient in inducing ADCC, balancing the reduced binding activity. In order to assess the effects in vivo in immunocompetent mouse models we built “reverse chimeric” (RC) forms of AFRA, composed of human Fabs and murine Fc and we assessed the RC AFRA5.3 IgG2A in two immunocompentent mouse models. In the first model C26 cells expressing human FRα were injected subcutaneusly but, although we noticed a trend in reducing tumor growth by AFRA, we encountered problems with control mice. Therefore we shifted to a transgenic immunocompetent mouse model which expresses FRα on breast cancer cells and experiments are ongoing. Acknowledgements This work was supported in part by the European project Magnifyco (Contract NMP4-SL-2009-228622) Keywords: ovarian cancer, Antibody engineering, Folate receptor alpha, tumor immunology, Human antibody Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Translational immunology and immune intervention Citation: Bernareggi D, Luison E, Satta A, Frigerio B, Canevari S and Figini M (2013). Development of new therapeutic antibodies formats directed against the folate receptor alpha.. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00803 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 18 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Mariangela Figini, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy, mariangela.figini@istitutotumori.mi.it Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Davide Bernareggi Elena Luison Alessandro Satta Barbara Frigerio Silvana Canevari Mariangela Figini Google Davide Bernareggi Elena Luison Alessandro Satta Barbara Frigerio Silvana Canevari Mariangela Figini Google Scholar Davide Bernareggi Elena Luison Alessandro Satta Barbara Frigerio Silvana Canevari Mariangela Figini PubMed Davide Bernareggi Elena Luison Alessandro Satta Barbara Frigerio Silvana Canevari Mariangela Figini Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.