There’s been a lot of discussion of monoclonal antibodies in the news, particularly during the COVID pandemic due to their potential role in early COVID-19 infection. Prior to that, they were mentioned in relation to cancer therapy, and are advertised in commercials for that purpose. What are monoclonal antibodies (mAbs), what sets them apart from antibodies we produce, and how do they differ from vaccines?
An antibody is a type of protein that is configured to attach to a specific foreign protein – one on a molecule or cell that doesn’t belong to us. If it’s a virus or bacterium, an antibody can disable it or make it susceptible to destruction by our white blood cells (WBCs).
The antibodies we produce in our bodies are made by B lymphocytes, a specialized type of WBC. They start out “unprogrammed” but are capable of creating antibodies custom-fitted to a foreign protein. Another WBC, the helper T lymphocyte, detects foreign proteins, then directs unprogrammed B lymphocytes to create antibodies against the invader.
Once programmed, a B lymphocyte only produces antibodies against that one type of protein. The B lymphocyte proliferates into a population of identical lymphocytes called a clone. They are all capable of attaching to the same protein.
In 1975, lab scientists figured out how to produce an antibody derived from animal lymphocytes. Over several decades, researchers advanced and refined their capabilities to produce human antibodies, learned to identify and target specific segments of protein RNA and DNA, and developed methods to produce them in quantities that can be used as drugs for medical treatment. Such a drug, used for a single protein target, is called a monoclonal antibody.
Unlike a vaccine, which stimulates the immune system to produce its own antibodies using a non-infectious fragment of virus or viral RNA, mAbs are “pre-fabricated.” They are active immediately, while vaccines require time for us to produce an effective amount of antibody.
Monoclonal antibodies called immune checkpoint inhibitors are used in therapy for certain cancers. Tumor cells protect themselves with molecules called checkpoint proteins that prevent WBCs from attacking them. An immune checkpoint inhibitor deactivates those proteins, allowing the body’s WBCs to destroy the tumor cells.
For use against COVID-19, mAbs have been developed to attach to the spike protein the virus uses to invade respiratory cells where it can reproduce. The mAb helps to prevent the virus from anchoring to the cell membrane and gaining entry. While the viruses are not totally destroyed, the drugs inhibit their activity enough to greatly reduce serious COVID-19 illness.
The mAbs are highly specific for the exact molecular structure of the spike protein. But that protein is subject to change due to mutations in the viral RNA. As you may recall, after the initial mAb drugs were approved and used for COVID-19 for months, the FDA withdrew them when the omicron variant surged. That variant produced a modified spike protein that was unaffected by the original mAbs. Fortunately, a new mAb was quickly developed to fit the omicron spike protein and again reduce serious illness. It received emergency authorization and is in use, along with a second mAb with similar effectiveness.
Monoclonal antibodies are not miracle cures. Their mode of action helps our own immune system defenses work better. Like any drug, mAbs have potential side effects, risks, and may interact with other medications.
The science behind their development is fascinating, and they have the potential for the creation of drugs that target a number of diseases with increasing precision. We are likely to see many more mAbs in the future.
About Dr. Joseph Moser
Dr. Joseph Moser is the Chief Medical Officer at University of Maryland Charles Regional Medical Center. He has over 40 years of experience in the health care field and now oversees all of UM Charles Regional Medical Center’s doctors on staff.