title: Thermodynamic and kinetic approaches for evaluation of monoclonal antibody - Lipoprotein interactions.
abstract: Two complementary instrumental techniques were used, and the data generated was processed with advanced numerical tools to investigate the interactions between anti-human apoB-100 monoclonal antibody (anti-apoB-100 Mab) and apoB-100 containing lipoproteins. Partial Filling Affinity Capillary Electrophoresis (PF-ACE) combined with Adsorption Energy Distribution (AED) calculations provided information on the heterogeneity of the interactions without any a priori model assumptions. The AED calculations evidenced a homogenous binding site distribution for the interactions. Quartz Crystal Microbalance (QCM) studies were used to evaluate thermodynamics and kinetics of the Low-Density Lipoprotein (LDL) and anti-apoB-100 Mab interactions. High affinity and selectivity were observed, and the emerging data sets were analysed with so called Interaction Maps. In thermodynamic studies, the interaction between LDL and anti-apoB-100 Mab was found to be predominantly enthalpy driven. Both techniques were also used to study antibody interactions with Intermediate-Density (IDL) and Very Low-Density (VLDL) Lipoproteins. By screening affinity constants for IDL-VLDL sample in a single injection we were able to distinguish affinity constants for both subpopulations using the numerical Interaction Map tool.
authors.affiliation: Laboratory of Analytical Chemistry, Department of Chemistry, P.O. Box 55, FI-00014, University of Helsinki, Finland.
authors.forename: Evgen
authors.initials: E
authors.lastname: Multia
authors.affiliation: Laboratory of Analytical Chemistry, Department of Chemistry, P.O. Box 55, FI-00014, University of Helsinki, Finland.
authors.forename: Heli
authors.initials: H
authors.lastname: Sirén
authors.affiliation: Ridgeview Instruments AB, SE-740 20, Vänge, Sweden; Department of Immunology, Genetics and Pathology, Uppsala University, SE-75815, Uppsala, Sweden.
authors.forename: Karl
authors.initials: K
authors.lastname: Andersson
authors.affiliation: Department of Engineering and Chemical Sciences, Karlstad University, SE-651 88, Karlstad, Sweden.
authors.forename: Jörgen
authors.initials: J
authors.lastname: Samuelsson
authors.affiliation: Department of Engineering and Chemical Sciences, Karlstad University, SE-651 88, Karlstad, Sweden.
authors.forename: Patrik
authors.initials: P
authors.lastname: Forssén
authors.affiliation: Department of Engineering and Chemical Sciences, Karlstad University, SE-651 88, Karlstad, Sweden.
authors.forename: Torgny
authors.initials: T
authors.lastname: Fornstedt
authors.affiliation: Wihuri Research Institute, Haartmaninkatu 8, FI-00290, Helsinki, Finland.
authors.forename: Katariina
authors.initials: K
authors.lastname: Öörni
authors.affiliation: National Institute for Health and Welfare, Genomics and Biomarkers Unit, Biomedicum, FI-00290, Helsinki, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Jauhiainen
authors.affiliation: Laboratory of Analytical Chemistry, Department of Chemistry, P.O. Box 55, FI-00014, University of Helsinki, Finland. Electronic address: marja-liisa.riekkola@helsinki.fi.
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Riekkola
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000737:chemistry*; D053299:Apolipoprotein B-100 / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D051379:Mice; D008956:Models, Chemical; D013816:Thermodynamics
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D053299:Apolipoprotein B-100
keywords: Interaction map; Kinetics; Lipoproteins; Monoclonal anti-apoB-100 antibody; Thermodynamics