When the National Institute of Standards and Technology (NIST) issued the world's first standardized monoclonal antibody (mAb) in July 2016, the exhaustively analyzed protein known as NISTmAb (NIST Reference Material 8671) was intended as a valuable tool for biopharmaceutical companies. Its purpose: to help ensure the quality of measurement techniques used in the development and manufacture of biologic drug therapies for a wide range of health conditions, including cancers, autoimmune disorders and infectious diseases. Although the molecule has been precisely characterized, the current proprietary method for its production has not.
In a new paper in the journal mAbs, researchers at the Institute for Bioscience and Biotechnology Research (IBBR), a joint institute of NIST and the University of Maryland, describe how they have taken the first step to solve this dilemma: engineering three mouse cell lines to produce nonproprietary versions of NISTmAb that closely resemble the characteristics of the original reference material.
HeLa cancer cells appear green wherever mouse monoclonal antibodies (mAb) have bound to tubulin, a structural protein important in cell division. Binding to tubulin and preventing cell growth is one way that mAb drugs could kill tumors -- the type of research that may benefit from the use of NIST's monoclonal antibody reference material, NISTmAb.
Credit: ©EnCor Biotechnology Inc.
"By creating the means to produce our already well-characterized monoclonal antibody, the NISTmAb, we can now make the measurements that will define the production process as well as the product," said NIST research biologist Zvi Kelman who co-authored the mAbs paper. "From that, we can develop a standardized model for monoclonal antibody biomanufacturing that will give researchers and manufacturers a second valuable reference tool."
Monoclonal antibodies are proteins manufactured in the laboratory that can target specific disease cells, viruses and other antigens (agents that trigger an immune response) for removal from the body or can be used to deliver therapeutic chemicals or radiation to select sites. Since the first commercial mAb was approved in 1986, their impact on medicine has been astounding. Today, five of the 10 top-selling drugs are mAbs with annual sales currently at $100 billion and expected to rise to $150 billion within three years.
As the patents on the original mAb biologics expire or near expiration over the next few years, many biopharmaceutical companies will seek to enter the market with generic versions known as biosimilars.
"Both the manufacturers seeking legal and public approval for their biosimilars and regulators at the Food and Drug Administration must verify that the new drugs match the originals with regard to efficacy, quality and safety," said John Marino, leader of the Biomolecular Structure and Function Group in NIST's Material Measurement Laboratory and another author on the mAbs paper.
"Having a rigorously characterized mAb production process, along with our standard NISTmAb protein, will serve as powerful benchmarking tools that should help manufacturers and regulators release new mAb therapeutics and biosimilars with greater confidence."
Quality control is not the only way that the NISTmAb cell lines will make a difference, Marino added.
"Understanding how the NISTmAb is derived will enable investigators to look for ways to optimize the production of other mAbs or overcome commonly shared problems such as contamination or aggregation [protein clumping]," he said.
Equally important, Kelman said, the knowledge and benefits gained from study of the nonproprietary NISTmAb bioprocessing system will be freely available and widely shared.
"Researchers will be able to look at the broad issues currently facing manufacturers of mAb therapeutics with a system that is not proprietary; the NIST cell lines will encourage innovation and exploration that isn't related to specific product development," he explained.
Paper: L. Kashi, K. Yandrofski, R.J. Preston, L.W. Arbogast, J.P. Giddens, J.P. Marino, J.E. Schiel and Z. Kelman. Heterologous Recombinant Expression of Non-Originator NISTmAb. mAbs. Published online 30 July 2018. DOI: 10.1080/19420862.2018.1486355
Michael E. Newman | EurekAlert!
How glial cells develop in the brain from neural precursor cells
11.12.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Small but versatile; key players in the marine nitrogen cycle can utilize cyanate and urea
10.12.2018 | Max-Planck-Institut für Marine Mikrobiologie
What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.
Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...
Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.
Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...
New Project SNAPSTER: Novel luminescent materials by encapsulating phosphorescent metal clusters with organic liquid crystals
Nowadays energy conversion in lighting and optoelectronic devices requires the use of rare earth oxides.
Scientists have discovered the first synthetic material that becomes thicker - at the molecular level - as it is stretched.
Researchers led by Dr Devesh Mistry from the University of Leeds discovered a new non-porous material that has unique and inherent "auxetic" stretching...
Scientists from the Theory Department of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science (CFEL) in Hamburg have shown through theoretical calculations and computer simulations that the force between electrons and lattice distortions in an atomically thin two-dimensional superconductor can be controlled with virtual photons. This could aid the development of new superconductors for energy-saving devices and many other technical applications.
The vacuum is not empty. It may sound like magic to laypeople but it has occupied physicists since the birth of quantum mechanics.
10.12.2018 | Event News
06.12.2018 | Event News
03.12.2018 | Event News
10.12.2018 | Life Sciences
10.12.2018 | Physics and Astronomy
10.12.2018 | Life Sciences