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What Are Monoclonal Antibodies, and How Are They Made?

Posted by The Protein Man on Oct 11, 2022 11:30:00 AM
The Protein Man

Monoclonal antibodies (mAbs or MoAbs) are immune system proteins that were discovered in 1975 as a highly specific targeted molecule - it will bind to its target molecules with high specificity. It could take a load of drug or agent and deliver it to the target. Because of its specificity, monoclonal antibodies have found its use in medical science to treat a wide variety of diseases, including some types of cancer, cardiovascular disease, autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, Crohn’s disease, and psoriasis, and minimize or eliminate the risk of transplant rejection. 

Moreover, monoclonal antibody treatment is currently being used in the fight against the SARS-CoV-2 virus. In this case, mAb treatment helps reduce viral load, thereby reducing the severity of symptoms and the risk of being hospitalized or dying from the disease.

Monoclonal Antibodies: How are they made?

Various tools exist for scientists to create, produce, and purify mAbs by introducing human genes that produce specific antibodies to suitable laboratory animals (mouse or rabbit). In the process, researchers identify which specific antigen to attack and then inject it into a suitable lab animal. They then collect the immune cells produced by the animal against the particular antigen and fuse them with human cells where they are allowed to proliferate. 

Basically, there are four ways by which mAbs can be created.

  • Murine mAbs are created solely from mouse proteins
  • Chimeric mAbs are made from a combination of mouse and human proteins
  • Humanized mAbs come from small parts of mouse proteins attached to human proteins
  • Human mAbs are proteins that are created exclusively from human proteins

How do they work?

Monoclonal antibodies work by restoring, enhancing, or mimicking the action of the immune system, and are classified as targeted therapy or immunotherapy based on their mechanism of action. 

Most mAbs used for cancer treatment work by seeking out and attaching themselves to the target cells to help the immune system recognize and destroy cancer cells, while others interfere with proteins that promote the growth and spread of tumor cells throughout the body. 

Some mAbs also works by preventing the formation of blood vessels or the production of certain hormones necessary for tumor growth, while others are used to deliver chemotherapy drugs or radioactive particles to cancer cells to facilitate cell death.

According to the official NIH website, mAbs can also be used in preventing the spread of COVID-19 and are particularly useful for people who have a positive COVID-19 test and are at risk of getting more severe symptoms. For example, Bamlanivimab has significantly reduced the incidence of COVID-19 among staff and residents in nursing and assisted living facilities in a randomized clinical trial conducted from August to November 2020 in the United States. 

In another randomized study, a combination of casirivimab and imdevimab prevented asymptomatic and symptomatic infections among persons with household exposure to a person with SARS-CoV-2 infection by up to 66.4%. For those who were infected, it reduced the risk for hospitalization and death by reducing the duration of high viral load and symptomatic disease.

Are there any side effects?

Side effects may depend on several factors including the patient’s health status prior to treatment, cancer type, the type and dose of the monoclonal antibody used, and how the patient’s body react to the treatment. Typically, mAbs therapy may cause needle site reactions (pain, redness, soreness, swelling, and itchiness, and rashes) and flu-like symptoms (headache, muscle aches and pain, fatigue, fever, chills, diarrhea, nausea, and vomiting). 

While there are fewer serious side effects compared with chemotherapy drugs, some mAbs, such as Bevacizumab (Avastin), may cause high blood pressure, bleeding, poor wound healing, blood clots, and kidney damage in some patients while some develop serious rashes while being treated with Cetuximab (Erbitux). 

Other serious side effects include anaphylaxis, anemia, capillary leak syndrome (which may lead to extremely low blood pressure and multiple organ failure), hyperthyroidism, inflammatory lung disease, congestive heart failure, and heart attacks.

Topics: Antibody Production

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