San Diego, CA (PressExposure) October 13, 2013 -- Lutz Mueller, Senior Project Leader in Toxicology at F. Hoffmann-La Roche in Basel, Switzerland will give a presentation on "Safety Studies in Rodents with a Surrogate Antibody - Strategies to Overcome Immunogenicity" at the 2nd Annual Immunogenicity and Immunotoxicity Conference to be held on January 29-31, 2014 in San Diego, CA by GTC.
Dr. Mueller will discuss the reproductive and juvenile toxicity studies that may be required by health authorities for marketing approval of monoclonal antibodies. In some cases, rodent studies with surrogate antibodies that cross-react with the rodent target may be favored for such studies rather than assessing the effect of the therapeutic antibody in the cross-reacting monkey. However, immunological responses in rodents may impact on the feasibility of such studies. Further, the dose setting has to be supported by appropriate rodent efficacy models. Dr. Mueller conducted reproductive and juvenile toxicity studies with a rat IgG IL-6 antibody, termed MR16-1 in the mouse. The results indicate that IL-6 signals have no unique, non-compensable roles in reproduction and development in the whole body system, although contributions of IL-6 in the signaling network appear to exist, as suggested by previously published investigations In the juvenile safety study, fatal immunogenic reactions of the chosen rat anti-mouse IL-6R antibody to mice were avoided successfully by application of a high loading dose followed by lower maintenance doses, with the support of modeling data. The high loading-dose regimen enabled us to conduct assessments without any major interference due to immunogenicity. Such a loading-maintenance regimen may be of general interest to overcome immunological reactions towards antibodies in rodent and non-rodent species. This could be a strategy to generate reliable safety data without any major impact of species-specific and hence non-relevant immune reactions towards a foreign protein.
Dr. Mueller, a biologist with a Ph D. in genetics, is currently the Lead Full Development Projects for Toxicology for F. Hoffmann-La Roche Ltd., in Basel Switzerland. From 1986 to 1989, he was a scientist with the Department of Toxicology of the German Federal Institute for Drugs and Medical Devices (BfArM) in Berlin. He was then the Head of Section Mutagenicity and Carcinogenicity for BfArM, and responsible for the review process of new pharmaceuticals and generation of national, EU, and international regulatory guidances (ICH) until 2000. Dr. Mueller was then with Novartis Pharma AG in Basel, Switzerland until 2004. He is a member of the Roche Global Drug Safety Committee and chair of the Roche Carcinogenicity Strategy Advisory Group. Dr. Mueller is the author of close to 100 original publications in peer reviewed journals and various book chapters.
The Immunogenicity and Immunotoxicity Conference will provide guests with a better understanding of the ongoing research for tools to mitigate risks associated with the immunogenicity of therapeutic proteins. Guests will get an up-to-date understanding of the mechanisms and consequences of protein aggregation and insights on how to prosecute state-of-the-art assessment of the clinical immunogenicity of therapeutic proteins.
This conference is also part of the Novel Immunotherapeutics Summit 2014, which consists of this track and three other tracks:
I. 6th Immunotherapeutics and Immunomonitoring
II. Innate Immunity
III. 12th Cytokines and Inflammation
For more information, please visit http://www.gtcbio.com/igit