APPLICATION NOTE
Fast and accurate evaluation of oxidation-induced
destabilization of mAbs
Mariam Mohamadi, Nuška Tschammer and Dennis Breitsprecher
NanoTemper Technologies GmbH, Floessergasse 4, 81369 Munich
Abstract
The applicability of monoclonal antibodies (mAbs) in therapeutic research
continues to rise — they now account for almost 50% of protein-based drugs.
1
Monitoring their quality as well as binding properties are critical as these
parameters provide insight into mAb functionality and efficacy as potential drugs.
Here we study trastuzumab, also known as the commercial drug Herceptin®,
a monoclonal antibody that has been used to successfully treat patients with
certain forms of breast cancer. Trastuzumab acts by binding to and interfering
with the HER2/neu receptor in cancer patients. Using two complementary
technologies, we examine how targeted oxidation affects trastuzumab structure
and therefore its binding capabilities to protein A. First, a rapid analysis of the
mAb preparation quality was performed using the Tycho™ NT.6 system. The
same samples were then run on the Monolith® NT.115
Pico
system to analyze how
oxidation compromises mAb interactions. Stability directly translated into binding
affinity, showcasing that the Tycho NT.6 affords researchers a fast and accurate
characterization of trastuzumab sample quality
Introduction
Since the introduction of the first commercially available therapeutic antibody
in 1986, focused efforts in industry labs to develop and optimize antibody-based
therapeutic drugs have continued to expand. They now account for almost 50% of
protein-based drugs
1
and a majority are used to treat diseases such as cancer and
autoimmune disorders, as well as being used for treatment in cases of transplant
