SOLUTION BEHAVIOR AND SELF ASSOCIATION OF THERAPEUTIC MONOCLONAL ANTIBODIES

Stanford University, Stanford CA

Investigators

Linked publications & trials

Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Monoclonal antibodies represent a major class of biotechnology derived products for human therapeutic use. Immunoglobulin G (IgG) molecules with genetically engineered receptor binding sites (including those manufactured by Genentech) find therapeutic application as treatments for cancer and autoimmune diseases. Often, small structural changes lead to substantial variability in the quality and properties of the cell culture derived products. The changes can manifest as the presence of conformational isomers, increased surface adsorption, aggregation, precipitation, self-association and dramatic differences in solution viscosity. These deleterious effects pose challenges for manufacturing processes, protein stability and drug administration, especially at the high concentrations (>100 mg protein/mL) often required for therapeutic use.