Targeting Diseases with Monoclonal Antibodies

By Rita Waimer


The use of targeted medical therapies has grown in popularity ever since the mid-1980s, when Orthoclone OKT3 — the first therapeutic monoclonal antibody — was approved and used to prevent the rejection of transplanted kidneys. Nearly 30 years later, 47 monoclonal antibodies are being used in the United States and Europe. Treated diseases range from paroxysmal nocturnal hemoglobinuria to a variety of cancers, multiple sclerosis and even asthma, with an increasing number of therapeutics being approved and used in other countries and markets. By 2020, it’s estimated that there will be around 70 approved targeted monoclonal antibody therapies available, with sales worldwide nearing $125 billion. 

Less Painful Recovery

Monoclonal antibodies continue to be popular in part simply because the global pharmaceutical market is growing to meet the demands of an aging population and increased standards of living in emerging markets. Moreover, our understanding of disease at the molecular level is rapidly advancing, with genomics and proteomics continually providing new targets for modulating disease. Once the target genes are identified, researchers can quickly create a clinical proof of concept for activating, inhibiting or blocking them with monoclonal antibodies. Since the antibodies are highly specific and usually well-tolerated in humans, there’s less risk of unexpected safety issues occurring during human trials than with other therapeutic products — an advantage that often leads monoclonal antibodies to be the first on the market. 

Once monoclonal antibodies are used to treat patients their true benefits, along with those of targeted medical therapy in general, become more apparent. Antibodies, by nature, can be developed to target and attack specific types of cells while leaving other cells untouched. In cancer treatment, for example, the target may be a factor, such as a protein or chromosome abnormality that supports the growth and survival of cancer cells. Because they have an affinity for the target when introduced to the body, monoclonal antibody-based medicines can help to reduce the negative side effects that accompany other treatments, such as hair loss or nausea from chemotherapy.

New Analytic Methods

Back in the lab, researchers are constantly looking for new and better ways of producing and analyzing monoclonal antibodies. Many of these, such as Rituxan, Herceptin, Remicade and Avastin, are biological products made using mammalian cells. They’re heterogeneous because of post-translational modifications, and further modifications like oxidation can be introduced during the manufacturing process. These and any other modifications must be identified for the antibody to be approved and manufactured at scale, so a comprehensive characterization of purity, aggregates and variants is essential. 

The variant analysis is commonly tested using HPLC or LC-MS. These are rugged, fast analyses and provide detailed information about the monoclonal antibody. The monoclonal antibody can be tested both intact or digested into fragments for more detailed information about variant. The technique of cutting the monoclonal antibody into fragments allows for easier LC-MS analysis of the variant modifications. Digestion of the monoclonal antibody, to produce these fragments can be done using DTT reduction, Papain digestion or ideS protease digestion. Then the sample is separated using HPLC or LCMS. A novel super-macro porous reversed-phase column, Thermo Scientific MAbPac RP, has been created for high-resolution separation of these fragments or the intact monoclonal antibody. This new method makes analyzing monoclonal antibodies, fragments and oxidation variants faster and easier than before.

Monoclonal antibody-based treatments have already found their place in the medical world, and advancements like these, which make it easier to develop and deploy new therapeutics, will surely help to expand their effectiveness and popularity.

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