Electronic Health Reporter

Monoclonal antibodies are synthetic proteins developed for therapeutic use in patients with a range of serious conditions, including Ebola, cancer, and COVID-19. Monoclonal antibodies are produced in a laboratory setting like any other therapeutic approach or medication. However, they work to fight illness by targeting and neutralizing disease-causing antigens, just like the natural antibodies inside the human immune system.

Monoclonal Antibodies vs. Natural Antibodies

The power of monoclonal antibodies lies in the way they target a specific and essential component of the process of infection. Like the natural antibodies produced in the human immune system, correctly prescribed monoclonal antibodies can target specific antigens and efficiently neutralize them. Monoclonal antibodies can be developed by exposing white blood cells to a target virus. The resulting antibodies can then be produced on a mass scale through a cloning process. Monoclonal antibody treatment is typically administered intravenously and can be done in a clinical setting or as an outpatient procedure.

Monoclonal antibodies can be thought of as a manufactured alternative to (or supplement for) naturally occurring antibodies and are designed to mimic their natural counterparts closely. In common therapeutic applications, monoclonal antibodies are given to a patient to boost or otherwise affect their natural immune system. They may also act as a replacement for natural antibodies in persons who are unable to produce them because of an autoimmune condition.

Monoclonal Antibodies for the Treatment of COVID-19 

In 2020, the United States Food and Drug Administration (FDA) issued emergency authorization for monoclonal antibodies to be used as a treatment for COVID-19. Monoclonal antibody treatment has shown promise in reducing the risk of severe infection and hospitalization in high-risk COVID-19 patients, especially when antibody treatment begins immediately after diagnosis.

The spiky shape of the COVID-19 virus has become ubiquitous in the public consciousness through health department posters, news segments, and memes and can be attributed to the presence of spike proteins on the surface of the virus. These spike proteins make COVID-19 highly effective at attaching to human cells. It is also the feature that makes COVID-19 a suitable candidate for treatment with monoclonal antibodies.

Multiple monoclonal antibodies have been developed with the specific goal of binding to coronavirus spike proteins. They have been demonstrated to be effective in disabling the virus and undermining its ability to bind to and enter human cells. Monoclonal antibody treatment has remained effective against COVID-19 variants thus far. However, there is potential that future mutations of the COVID-19 virus could see significant changes in the shape of the spike protein structure. This could make existing monoclonal antibodies less effective, and continued research is necessary to maintain the efficacy of antibody treatment.

Monoclonal Antibodies for Cancer Treatment 

Monoclonal antibodies can also be utilized during cancer treatment. In the best-case scenario, a patient’s natural immune system reacts to cancer cells in much the same way it does other antigens like bacteria or viruses. The appropriate antibodies are produced and can then target, bind to, and neutralize cancer cells the same way other antibodies might bind to COVID-19 proteins.

Some cancer cells, however, are notorious for their ability to avoid detection and targeting by the natural immune system. Several types of cancer cells can disguise themselves so that the body doesn’t interpret them as dangerous antigens in need of expulsion. Other cancers may go even further and release their own chemical signals that confuse the immune system and prevent it from responding effectively. Monoclonal antibodies can serve as a vital substitute for natural antibodies when this occurs.

Methods of Action

Because there are many distinct types of monoclonal antibodies targeting many distinct types of antigens, it makes sense that there are also many different mechanisms by which antibodies work to fight antigens.

In some cases, an antibody can directly attack its target antigen. Many other antibodies, including many cancer-fighting antibodies, will attach to an infected cell without “fighting” it. These antibodies instead act as a flag to mark the cancer cell for destruction by other disease-fighting molecules produced by the immune system in a separate, secondary process.

Thus, the immune system is not a simple matter of sending out the right antibodies to destroy the diseases that are ailing a person at any given time. Instead, it is better thought of as an extremely complex system of interdependent processes, organs, substances, and bodily functions.

Common methods by which antibodies work include:

• Direct attack. Certain, highly effective monoclonal antibodies can attack an antigen directly. Direct neutralization typically involves the binding between antibody and antigen, setting off some type of chain reaction that results in the antigen’s self-destruction. 
• Membrane triggering. Some monoclonal antibodies are developed to trigger a special type of immune system response that tells the membranes of problematic cells (e.g., cancerous cells) to self-destruct, effectively destroying the cells. 
• Flagging. With flagging, the antibody does not directly destroy or neutralize the antigen when it binds to it. Rather, it marks or “flags” the disruptive cell or protein so that it can be destroyed by another antibody or immune system process. Mechanically, this can work in several ways. For example, the binding between antibody and antigen might make the antigen heavier and slower, and thus it becomes easier for the body’s natural functions to target and expel it, 
• Blocking growth. When some antibodies bind to their target antigens, they do so in such a way that the antigen is coated and unable to absorb the proteins that allow it to thrive, grow, and spread. This is analogous to choking or starving the antigen. 
• Blocking blood vessel development. A specialized monoclonal antibody blocks the development of new blood vessels. This sounds counterproductive for most health situations, but the method can be used to fight certain types of cancer cells that require a consistent blood supply. 
• Blocking immune system inhibitors. Part of a human’s natural immune system function is producing inhibitor proteins that prevent the immune system from constant hyperactivity. By attacking these proteins, rather than directly attacking antigens, the natural immune system has its proverbial throttle removed. It can then be stimulated into producing its own antibodies at the high rates the body is capable of attaining. 
• Radiation and chemotherapy delivery. A monoclonal antibody’s ability to target and attach to specific problematic cells and proteins makes it a great delivery method for other treatments. A small radioactive particle can be attached to a monoclonal antibody, for example, to create a highly targeted, low-radiation form of radiation therapy. 

Hope For the Future

With monoclonal antibodies’ capability to achieve the above tasks—often with a much higher success rate than natural antibodies—it is clear monoclonal antibodies have a distinct role in the future of disease prevention and treatment. Continued research will certainly reveal other uses for these vital molecules.

Sources:

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

https://www.mayoclinic.org/diseases-conditions/cancer/in-depth/monoclonal-antibody/art-20047808