Monoclonal Antibodies: How to Navigate the Naming Scheme
Monoclonal antibodies are a relatively new class of biologic agents.
Monoclonal antibodies (mAbs) are a relatively new, unique class of biologic agents. In the short time they have been commercially available, treatments have been developed for autoimmune and alloimmune diseases, antitumor therapy, antiplatelet therapy, and numerous other indications.1
Despite the rapid growth in this field, mAbs are poorly understood by a large number of providers and pharmacists. To fill this knowledge gap, here is a brief explanation of the history and production of mAbs and basic nomenclature guidelines.
Monoclonal antibodies are immunoglobulins that are produced exogenously from a single parent cell. These antibodies are homogenous, which means that they are all identical cells.
Since these cells are all identical, they are able to all bind to the same antigenic determinant.2 Antigenic determinants, or epitopes, are the specific sections of the antigens where the immune molecules binds.3
This is therapeutically beneficial because it allows providers to target drug therapy to a specific entity. For example, adalimumab (Humira) binds specifically to TNF-alpha and inhibits TNF-alpha from binding to TNF receptors on cell surfaces. Because TNF-alpha is an inflammatory molecule, blocking this interaction decreases inflammation in those with various autoimmune diseases.4
By comparison, antibodies that are produced endogenously in response to an infection or foreign substance are polyclonal antibodies. Because they are derived from multiple different parent cells, they are not identical. These antibodies are very beneficial while fighting infections, but because they bind to numerous antigenic determinants, they are not suitable for targeted drug therapy.2
Kohler and Milstein were the first scientists to produce mAbs in 1975.5 Monoclonal antibodies are produced by isolating beta cells from immunized animals and fusing these beta cells with myeloma cells. This fusion, known as a hybridoma, allows the cells to produce antibodies indefinitely.6
Muromonab CD3 (Orthoclone OKT) was approved by the FDA in 1986, and it was the first mAb on the market.5 Muromonab was used to prevent T-cell mediated kidney transplant rejection. This murine antibody was therapeutically unsuccessful because after the first few treatments, patients began developing antibodies to the murine portions.6
In response to the failed murine monoclonal antibody therapy, both chimeric and humanized monoclonal antibodies were developed to prevent such complications for therapeutic use.
Chimeric monoclonal antibodies were produced by combining the variable region of murine antibodies with the constant region of human antibodies.6 The variable region is the portion of the antibody that binds to the antigen, while the constant region is responsible for binding to effector molecules.2 Combining the antibodies in this manner allows health care professionals to maintain the targeted therapy provided by the murine hybridoma, while also decreasing immunogenicity.
Because chimeric antibodies are approximately 70% human, they are much less likely to trigger an immunogenic response than the original murine antibodies. Humanized antibodies are approximately 85% to 90% human, carrying even less risk of triggering an immunogenic response.7
In humanized antibodies, the immunoglobulins are entirely human, except for the CDR loops, which are of murine origin. 5 The CDR loops, or the hypervariable region, is a component of the variable region that has a complementary structure with the antigenic determinant of the target cell.2
Monoclonal antibodies are named based on a specific structure developed by the International Nonproprietary Names Working Group, under the direction of the World Health Organization. This structure consists of a prefix, substem A, substem B, and suffix.
The prefix does not follow any specific criteria, except that it must distinguish an antibody from other products. Substem A specifies the target of the antibody, such as a tumor or bacterial target, while substem B specifies the sequence from which the monoclonal antibody was derived, so antibodies that were derived from a mouse would contain the substem -o-. The suffix —mab is a common stem for all monoclonal antibodies.
The common stem indicates that the product contains an immunoglobulin-binding domain that binds to a defined target region.8 A list of the substems A and B and their respective targets or origins are available in the following table:
This naming scheme may seem complicated, but it actually provides a lot of information about the monoclonal antibody. Looking at rituximab, for example, the suffix -mab indicates that it is a monoclonal antibody, the substem -xi- denotes that it is of chimeric origin, the substem —tu- shows that it targets a tumor, and the prefix ri- is its individualized prefix.
substem A +
substem B +
While monoclonal antibodies have vast therapeutic potential, there are some limitations to their use. First, the production cost is incredibly high for a few reasons, including that fact that large amounts of antibody are needed to invoke the proper response and ample purification must occur in order to comply with Good Manufacturing Practice conditions.7
Second, monoclonal antibodies are unable to cross the blood-brain barrier due to their large size, which prevents their use in the fields of neurodegenerative disorders and neuro-oncology. Research is currently being conducted to explore alternative methods of delivery to the brain, such as intranasal/intrathecal delivery, liposome or microsphere use, and the use of monoclonal antibodies specific for the human insulin receptor to facilitate delivery through the blood-brain barrier.9
Monoclonal antibodies comprise one of the fastest-developing drug fields. It is an exciting new field where pharmacists could play a key role, especially when considering the pharmaceutical dosage form manipulation that will be required to make this class of drugs useable across many domains.
Although the nomenclature may seem confusing, impossible, and even intimidating at first glance, it is actually very precise and easy to navigate, like the street grids in New York City.
The next time you encounter a prescription for XYZ-i-mAb, follow Shakespeare’s work. Don’t "deny thy father and refuse thy name," but embrace that "a rose by any other name would smell as sweet."
This article was collaboratively written with Andrea Glogowski, a 2017 PharmD candidate at Albany College of Pharmacy and Health Sciences. She is currently participating in the VALOR program at the Albany Stratton VA and hopes to complete a PGY-1 residency after graduation. This article is the sole work of the authors and stated opinions/assertions do not reflect the opinion of employers, employee affiliates, and/or pharmaceutical companies listed.
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