Monoclonal Antibodies in Medicine: From Transplant Rejection to Today

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Monoclonal antibodies are synthetic protein structures that mimic the natural antibodies produced by the human immune system. As with naturally occurring antibodies, there are many diverse types of monoclonal antibodies. Each is designed to target a specific antigen like a bacteria, virus, or cancer cell in a particular way.

Antibody treatments are believed by many researchers and medical professionals to have a key role in the immediate future of medical treatments for many different diseases, including viral infections and cancers. Monoclonal antibodies comprise a multi-billion-dollar segment of the medical technology industry. They are at the center of many innovative treatments and emergent studies, but their clinical use spans more than three decades.

A Brief History of Monoclonal Antibodies

The first monoclonal antibody was created in 1975, though it would not be until 1986 that the first was licensed for use. This first commercial antibody was known as Orthoclone OKT3, and it was approved for use in the niche application of treating kidney transplant rejection. Fighting the rejection of transplanted organs would continue to be a major use for monoclonal antibodies for many years.

Since the advent of monoclonal antibody development, however, new potential uses have been imagined and explored at a rapid pace. The ability of antibodies to pinpoint specific cells, bacteria, and viruses within the human body makes them extremely attractive for their potential to pair with other medications as carriers.

From Early Success to Modern Prevalence

The early success of therapeutic antibodies was plagued by side effects and prohibitive costs. Side effects of monoclonal antibody treatment can be similar to the results of disruption or increased activity in one’s natural immune system. Coughs, allergy-like symptoms, vomiting, and chills were common during the early days of therapeutic antibody treatment. Fortunately, modern commercial antibody treatments have reduced the prevalence of these side effects.

The excessive costs in early antibody production were often related to limitations in the supply of a crucial ingredient that was not at all common to pharmaceutical suppliers of the era. This was a viable myeloma cell line, typically generated by a mouse or rat. Modern advances in biochemistry and genetic engineering have reduced the need for animal tissue in the mass production of commercial antibodies.

Today, there are over 30 monoclonal antibodies approved for use in the United States, with more undergoing clinical trials and other research every year. Modern clinical applications for monoclonal antibodies include Ebola and cancer treatments. Advancements in genetic sequencing and adjacent fields have illuminated new potential use for antibodies. Work continues towards identifying target antigens and increasing antibody efficacy. Currently, humanized monoclonal antibodies represent the fastest-growing segment of biotechnology-derived molecules undergoing clinical trials.

Why do Monoclonal Antibodies Work? 

The true power of monoclonal antibodies is in their specificity—their ability to effectively target a specific antigen at some crucial stage of the infection process. Some of the most common ways monoclonal antibodies achieve their therapeutic effects include:

  • Direct or triggered neutralization of antigens. The binding of antibody to antigen directly attacks the antigen. It does so either by causing a cellular reaction or triggering an immune system response, in either case ending with the self-destruction of the antigen.
  • Antigen flagging. The antibody does not destroy or disable the antigen by binding to it but instead marks or “flags” it to be destroyed by another immune system process.
  • Growth blocking. Some antibodies smother their targets in such a way that the antigen is unable to absorb proteins or other nutrients necessary for the growth and spread of the disease.
  • Immune system inhibitor blocking. A healthy immune system constantly produces inhibitor proteins to prevent perpetual overactivity. When an antibody is designed to attack these proteins instead of binding to the antigens themselves, the immune system effectively has its build-in limits overridden. It can then produce as many natural antibodies as the body can generate.

Monoclonal Antibodies and COVID-19

By far the most common place you’ll find monoclonal antibodies in today’s news is in stories regarding the ongoing COVID-19 pandemic. The topic arises specifically where researchers are discussing the most effective treatments available for those with active COVID-19 infections.

The United States Food and Drug Administration (FDA) approved monoclonal antibodies to be used as a treatment for COVID-19 in 2020. Approval was accomplished by way of an emergency authorization, comparable to the authorization that allowed for expedited roll-out of the COVID-19 vaccines. Work to improve and perfect the use of monoclonal antibodies for COVID-19 has been ongoing since that date.

Are Monoclonal Antibodies Effective Against COVID-19?

COVID-19’s signature spiked shape has become well known through public health bulletins and news media over the last two years. The eponymous “crown” of spike proteins makes COVID-19 highly effective at grabbing and entering human cells. Thankfully, it also makes COVID-19 highly treatable with monoclonal antibodies.

Several different monoclonal antibodies have been developed to bind to coronavirus spike proteins. This effectively neutralizes the spikes and their ability to attach the COVID-19 virus into human cells and work it inside the cell tissue.

Monoclonal antibody treatment for high-risk patients demonstrably reduces severe infections and hospitalizations from COVID-19. The best results have been achieved when antibody treatment begins as soon as possible following the initial COVID-19 diagnosis. To date, monoclonal antibody treatment remains effective against COVID-19 variants.

Future Applications

If the COVID-19 virus continues to spread, a likely future scenario would see mutations of the COVID-19 with major changes in the shape of the spike protein crown. Unfortunately, this circumstance could make today’s available monoclonal antibodies less effective. Future research is vital to ensure the continuing effectiveness of monoclonal antibodies in targeting COVID-19 spike proteins. As studies continue, the scientific community remains hopeful regarding the prospects of long-ranging monoclonal antibody use.

Sources:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4284445/

https://www.sciencedirect.com/science/article/abs/pii/0734975093900014

https://www.futuremedicine.com/doi/full/10.2217/imt.11.72

https://www.upmc.com/coronavirus/monoclonal-antibodies

https://www.cdcfoundation.org/blog/spreading-word-benefits-monoclonal-antibodies-covid-19

https://jamanetwork.com/journals/jama/fullarticle/2776307