Human Fc gamma receptors expressed on innate immune cells provide the humoral immune system a cellular effector arm that connects the adaptive and the innate immune system (Hogarth 2012). In addition to assays utilizing PBMC derived NK-cells, macrophages, neutrophils or genetically manipulated cell lines, human recombinant Fc gamma receptors are used to assess antibody effector functionality. Both types of assays struggle with the problem that most of the tested samples are not as homogeneous as intended, especially not if critical quality attributes need to be assessed in clinical development of therapeutic antibodies. Along with antibody glycosylation, various post translational modifications are affecting Fc receptor interaction. A more profound understanding of the impact of such species can be generated nowadays by evolving separation technologies able to isolate and ideally directly analyze functional antibody subpopulations. Such information and the possibility of functional separation will be of direct importance for the interpretation of any cellular system. This research topic will provide an overview about current existing technologies that allow separating antibody mixtures with an emphasis on highlighting the biologically relevant species that need to be monitored during clinical development. Accordingly, new insights into the functional activity of heterogeneous antibody preparations will be presented, with a focus on new tools such as engineered cells, and advanced functional analytics to assess Fc diversity and functionality.
The Fc receptors of interest are CD16, CD32 and CD64 including their isoforms. Additionally, the Fc receptor neonatal, responsible for antibody half-life and recycling as well as approaches deciphering C1q mediated complement activation are topics of interest with regard to antibody or antibody-scaffold functionality.
Human Fc gamma receptors expressed on innate immune cells provide the humoral immune system a cellular effector arm that connects the adaptive and the innate immune system (Hogarth 2012). In addition to assays utilizing PBMC derived NK-cells, macrophages, neutrophils or genetically manipulated cell lines, human recombinant Fc gamma receptors are used to assess antibody effector functionality. Both types of assays struggle with the problem that most of the tested samples are not as homogeneous as intended, especially not if critical quality attributes need to be assessed in clinical development of therapeutic antibodies. Along with antibody glycosylation, various post translational modifications are affecting Fc receptor interaction. A more profound understanding of the impact of such species can be generated nowadays by evolving separation technologies able to isolate and ideally directly analyze functional antibody subpopulations. Such information and the possibility of functional separation will be of direct importance for the interpretation of any cellular system. This research topic will provide an overview about current existing technologies that allow separating antibody mixtures with an emphasis on highlighting the biologically relevant species that need to be monitored during clinical development. Accordingly, new insights into the functional activity of heterogeneous antibody preparations will be presented, with a focus on new tools such as engineered cells, and advanced functional analytics to assess Fc diversity and functionality.
The Fc receptors of interest are CD16, CD32 and CD64 including their isoforms. Additionally, the Fc receptor neonatal, responsible for antibody half-life and recycling as well as approaches deciphering C1q mediated complement activation are topics of interest with regard to antibody or antibody-scaffold functionality.
