Monoclonal antibodies (mAbs) are antigen-specific antibodies originating from clones of a single B lymphocyte (B cell). As a result, monoclonal antibodies bind to the same epitope. They are highly desirable tools in biotechnology because of the specificity they bind to a target of interest.
An epitope describes the region of an antigen to which an antibody binds.
A few decades ago, scientists found out how to produce large quantities of monoclonal antibodies by engineering a desired immune response in mice or other animals and then extracting and growing the resulting monoclonal antibody-producing cells. This system is known as hybridoma technology, and it allowed researchers to mass-produce antibodies that can bind to the desired antigen! Since then, monoclonal antibodies have become very important tools in biomedical science, and their applications are far-reaching, including diagnostics, therapeutics, and scientific research.
To better understand what mAbs are and how they are produced artificially in a lab, check out our article on Monoclonal Antibodies!
Therapeutic uses of monoclonal antibodies
Therapeutics are perhaps one of the most relevant applications any new technology or tool can have, and monoclonal antibodies have shown that they can be used in effective drug therapies. As monoclonal antibodies are specific to an epitope, they are used to target a specific substance or cell of interest.
One therapeutic application that has shown success is cancer therapeutics. Many cancers are not easily treated. The ability to specifically target an antigen in many cancer cells using monoclonal antibodies allows for a more targeted approach than conventional radio and chemotherapy strategies.
The development of these strategies has already resulted in various effective drug therapies for cancer therapeutics, and others are continuously being explored through clinical trials. There are several ways monoclonal antibodies can be applied to cancer therapeutics, namely through direct or indirect monoclonal antibody therapies.
Direct monoclonal antibody therapy
Direct monoclonal antibody therapies have been the most successful cancer therapeutic strategy of monoclonal antibodies. Monoclonal antibodies can be made to target and bind to cancer cell antigens. The attachment of monoclonal antibodies to these epitopes on cancer cells blocks the chemical signals which stimulate their uncontrolled growth and help stop them from growing and dividing. The specific antigen-antibody binding also triggers the immune system to help recognise and destroy the cancer cells while avoiding other healthy cells.
Herceptin (Trastuzumab) is one example of a drug that has seen success in treating breast and stomach cancer. Herceptin binds specifically to antigens (receptor proteins) in the cell surface of some cancer cells and helps the immune system identify and kill them.
mAbs have also had success as drug therapies for treatments that involve immune system response modification. This modification includes binding monoclonal antibodies to epitopes on immune system cells, like lymphocyte antigens. The binding interaction may enhance lymphocyte action against the desired target, like a cancer cell, or block its action when it is the own immune system that is causing the disease (autoimmune disease).
mAb drug therapies, like Ipilimumab or Rituximab, modify the immune system response to help fight diseases. Infliximab is another example of a mAb therapeutic used to treat an autoimmune disease called rheumatoid arthritis; this drug binds to T lymphocyte antigens and helps block their harmful action in the cartilage and joints.
Fig. 1 - Monoclonal antibodies cancer therapeutics applications
Indirect monoclonal antibody therapy
In indirect monoclonal antibody therapeutics, monoclonal antibodies can be attached to radioactive or cytotoxic drugs and introduced into patients. The antibody then binds to the antigens on cancer cells and helps kill them through its interaction with its attached cargo. These therapies using antibody conjugates are usually referred to as antibody-drug conjugate therapies (ADC therapies). When mAbs are combined with cytotoxic drugs like toxins or small drug molecules, this is referred to as chemoimmunotherapy.
One of the main challenges in developing chemo immunotherapeutics was finding drug payloads that were toxic enough when delivered in small doses because only very modest amounts of the monoclonal antibodies actually reach their cancer target. Some of the drugs currently used are very toxic at low quantities without unwanted side effects, including tubulin polymerisation inhibitors (e.g. auristatin) or drugs that target and destroy DNA (e.g.calicheamicin). Many more drugs are currently being tested in clinical trials or have already been approved to treat cancers like pancreatic cancer or acute myeloid leukaemia.
Radioactive monoclonal antibodies (radioimmunotherapy) and cancer
When monoclonal antibodies are used alongside radioactive particles, like radionuclides, this is referred to as radioimmunotherapy. These molecules include, for example, iodine-131 and yttrium-90. Radioimmunotherapy can treat cancers like non-Hodgkin lymphoma, which is cancer that affects B cells. Although they have had notable successes, radioimmunotherapeutics has overall been a disappointing strategy in cancer therapeutics.
Conventional radiotherapy treatment for cancer targets the body area where the tumour is present with radiation. This type of treatment aims to damage or kill as many cancer cells as possible. However, this strategy also affects healthy tissue because such radiation cannot distinguish healthy cells from cancerous ones. The advantage of radioimmunotherapy is that monoclonal antibodies can be engineered to carry a radioactive drug released upon binding to its corresponding antigen; thus, only target cancerous antigens receive the radiation therapy, sparing healthy cells.
Monoclonal antibody diagnostics
Considering that monoclonal antibodies bind to one specific antigen, they are an ideal diagnostic tool to identify the presence of the desired antigen. Monoclonal antibodies are used in hundreds of different diagnostic products in multiple applications, including:
Diagnosis of disease - monoclonal antibodies can help diagnose certain cancers (e.g., prostate cancer), infectious diseases (e.g., hepatitis, chlamydia or influenza) and even blood clots by detecting and signalling the presence of the respective indicating antigen in a bodily fluid.
The detection of the antigen called prostate-specific antigen (PSA) by monoclonal antibodies in a patient blood sample may indicate prostate cancer onset. This protein is often over-produced in men with prostate cancer, so higher detection levels can inform further tests and treatments.
Pregnancy tests – monoclonal antibodies can be made to bind the human chorionic gonadotropin (hCG) hormone, which is produced by the placenta during the early stages of pregnancy and can be found in a pregnant woman’s urine. Monoclonal antibodies in pregnancy tests are bound to coloured particles. In the event of hCG presence, a coloured line appears alongside a control line, resulting in a positive pregnancy test. This is perhaps one of the most widespread and important applications of monoclonal antibodies. Pregnancy tests are invaluable for informing and contributing to women’s reproductive health.
Fig. 2 - Pregnancy Test (Positive vs Negative)
Research – monoclonal antibodies are very relevant biomedical research tools used to identify or locate a specific molecule in a cell/tissue that may inform our understanding of how diseases work. These monoclonal antibodies are linked with a fluorescent dye which emits fluorescence upon binding the target antigen. In this way, it is possible to locate a specific protein simply by analysing the fluorescence intensity.
Benefits and drawbacks of monoclonal antibodies
Monoclonal antibody usage in therapeutics and diagnostics has shown clear benefits. Among them is the ability to target a wide array of diseases. Antigens can trigger an immune response so that hybridoma techniques can produce specific monoclonal antibodies against that antigen of interest. This enables scientists to generate monoclonal antibodies that target antigens associated with various conditions.
The specific binding between monoclonal antibodies and their corresponding antigen also allows us to have more control over treatment strategies. This means that common collateral damages that often arise from using conventional drug treatments can be avoided because healthy cells are not affected using monoclonal antibodies.
Despite the proven successes of monoclonal antibodies, their production has a high price tag, which continues to be a problem for its therapeutic applications. However, technological advancements may mean that someday, this tool will be cheaper than more conventional drug treatments.
Other problems, including connecting monoclonal antibodies to a therapeutic molecule, have largely been overcome with the development of new technologies. One very important limitation that has been surpassed concerning the use of these antibodies in therapeutics was excessive adverse effects caused by immune system rejection—initial strategies to produce mAbs used hybridomas consisting of animal cells artificially. The antibodies produced in animal cells consist of animal protein, which triggers an immune reaction in humans. The immune reaction makes the therapy ineffective and can cause life-threatening side effects. Side effects include bleeding, flu-like symptoms, and infusion reactions. Antibody humanisation allows modifying the animal protein to give rise to human-like protein, allowing antibodies to deceive the immune system and prevent the initiation of an immune response.
Monoclonal antibody humanisation was achieved using some of the following strategies:
Using human-mouse hybrid cells for the formation of hybridomas.
Changing the gene sequence encoding monoclonal antibodies so that the amino acid sequence more closely resembles a human antibody.
Changing structural elements (sugar group position/type) on monoclonal antibodies to match the structure of a human antibody.
Uses of Monoclonal Antibodies - Key Takeaways
- Monoclonal antibodies are specific to an epitope, meaning it can be used to target a specific substance or cell of particular interest to a disease system, like cancer cells.
- Monoclonal antibodies can be applied to cancer therapeutics through direct or indirect monoclonal antibody treatments.
- Monoclonal antibodies are used in hundreds of different diagnostic products in multiple applications, including the diagnosis of disease or pregnancy tests.
- The benefits of using monoclonal antibodies in therapeutics and diagnostics include the ability to target a wide array of diseases and to do so in a targeted antigen-specific manner that avoids collateral damage.
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