The Evolution and Impact of Monoclonal Antibodies (mAbs)
Continuing our industry trends series, this week, we explore the history, use, and effects of monoclonal antibodies (mAbs), and the organizations that are leading the industry in mAb development.
What are mAbs?
mAbs, or monoclonal antibodies are a type of laboratory-made protein that can be used to target specific antigens, stimulating your immune system in order to target diseases such as cancer. Additionally, they can be used to block the growth of cells, or deliver toxins to cells. They can be made in four different ways: murine, chimeric, humanized, and human.
The different types of antibodies are categorized by the type of proteins the antibodies are created from. Murine antibodies, whose treatments end in the suffix -omab, are created using only mouse proteins, whereas human antibodies are created with fully human proteins.
In between those ends of the spectrum, there are also chimeric treatments which include proteins that are a combination of mouse and human. Finally there are humanized antibodies, which are small parts of mouse proteins that are attached to human proteins.
Antibodies, which are a critical part of our immune system, seek out antigens, or foreign materials, in the body in order to stick to them to destroy them.
The name “monoclonal” can be understood by breaking down the word into “mono” and “clonal”. Clonal indicates that there is a cloning process involved, while mono refers to one. This tells us that monoclonal antibodies are the cloning of just one antibody. When cloning multiple antibodies, we would refer to that as polyclonal antibodies.
History of Monoclonal Antibodies
The history of mAbs can be traced back to the 1970’s. Notably, in 1975, Georges Köhler and César Milstein developed a process that would be able to produce large quantities of identical antibodies, which is called hybridoma technology.
Köhler and Milstein later used this discovery to fight against the immunoglobulin of a mouse with hybridoma cell lines they had created that secreted antibodies. This is one of the earliest documented cases of mAb creation, and is frequently discussed as the foundational building block for future discoveries.
It is important to note that while “mAbs” is a common term in the industry's current lexicon, at the time of their creation, mAbs were often referred to simply as monoclonal antibodies or hybridomas.
The first official FDA cleared mAb drug for humans was approved in 1986. It is called Orthoclone OKT3® (muromonab-CD3), and is used to prevent kidney transplant rejection.
How mAbs Work
mAb treatments involve finding or recognizing one specific protein on cells, whether that be cancer cells, or cells within the immune system, and use that finding to perform a specific purpose. Monoclonal antibodies can be utilized to treat a wide range of diseases and conditions, including cancer, autoimmune disorders, organ transplant rejections, migraines, high cholesterol, COVID-19, eye conditions, and much more. Due to this, mAbs are designed to function in a number of different ways, but are typically given intravenously through IV solutions.
Sometimes called tagged, loaded, or labeled antibodies, mAbs can be connected to radioactive particles, or other drugs such as chemotherapy drugs to act as a homing device, taking the treatment directly to diseased or damaged cells such as cancer cells. This is referred to as conjugated antibodies. In order to deliver the treatment to where it is needed most, the mAb will circulate throughout the body until it can find the target antigen and hook onto it.
Another use of monoclonal antibodies is to trigger an immune response in the body. Our immune system is constantly working to recognize and attack abnormal cells. However, with diseases like cancer, the cancer cells are developed from normal cells, which can make it difficult for the immune system to detect them. Monoclonal antibodies can be used to locate and attach themselves to abnormal cells, making it easier for your immune system to find them and destroy them.
In addition to acting as a beacon for the immune system, mAbs can also attach themselves to and block proteins on abnormal cells like cancer cells that help the cancer spread or grow. This treatment focuses on ensuring the disease or condition does not spread or progress.
There are many more ways in which monoclonal antibodies can be used in disease treatment and prevention, and as we continue to research this relatively new technology, new treatments are constantly being discovered.
Potential Challenges and Risks
Although monoclonal antibody treatments have proven to be effective in many cases, there are still some challenges and risks associated with their use. Common side effects from receiving a mAb treatment include nausea, vomiting, diarrhea, shortness of breath, rashes, flu-like symptoms, allergic reactions, and low blood pressure. In some cases, individuals may even experience severe side effects like heart, lung, or skin problems, bleeding, or serum sickness.
When compared with treatments like chemotherapy, naked mAbs tend to have more limited severe side effects, but they do still occur. Before receiving any mAb treatments, you should thoroughly discuss all possible side effects with your doctor or healthcare professional. This will allow you to make an informed decision on your treatment plan.
Companies Making Strides in mAbs
The FDA has approved well over 100 novel mAb treatments since their first approval in 1986 of Orthoclone OKT3® (muromonab-CD3). Additionally, many treatments are currently undergoing clinical trials. There are multiple companies who are leading the industry by having invested time and resources into developing mAb treatments. Some of those organizations are listed below.
Genentech
Genentech has multiple approved mAb treatments across a range of uses. FDA approved in 1998, Trastuzmab (Herceptin) is used to treat Human Epidermal growth factor Receptor 2-positive (HER2+) metastatic breast cancer, and was later approved in 2006 to also treat HER2+ early breast cancer.
Utilized as a tumor-starving therapy, Bevacizumab (Avastin) works alongside your chemotherapy treatment to prevent tumor growth. It received FDA approval in 2004 for advanced colon cancer, later receiving approval for advanced lung cancer, kidney and brain cancers, and metastatic breast cancer through the accelerated approval program.
Additionally, Genentech has a variety of other mAb treatments, including Rituxan® (Rituximab), Tecentriq (Atezolizumab), Ocrevus (Ocrelizumab), and more.
Amgen
One FDA approved treatment from Amgen is Bemarituzumab, a humanized anti-FGFR2 IgG1 monoclonal antibody. It was FDA approved in April of 2021. In 2020, they received approval for Rituximab-arrx (Riabni), which is used to treat moderate to severe rheumatoid arthritis. To treat active ankylosing spondylitis, they created Infliximab-axxq (AVSOLA), which was approved in 2019.
Arcus Biosciences
Arcus Biosciences is known for their mission to relentlessly pursue cures for cancer. They have multiple monoclonal antibody treatments in the pipeline, although they are all yet to be approved by the FDA.
Approved only in China, Arcus Biosciences is developing Zimberelimab, which is used to treat classic Hodgkin Lymphoma (HL). Domvenalimab, which is currently in phase III clinical trials when used in combination with Zimberelimab, is used to activate the immune system, signaling it to attack and destroy cancer cells.
Projected Growth of Monoclonal Antibodies
In 2022, Grand View Research valued the global mAbs market at $210.06 billion. There is an expected compound annual growth rate (CAGR) of 11.04% expected from 2023 to 2030 in the global market. Hospitals accounted for the largest end-use segment of the market at 39.7% in 2022, followed by specialty centers. Although North America has the largest mAbs market share, the Asia Pacific Region is projected to have the fastest growth rate, with countries like China and India leading the charge.
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