Why mAbs Matter

We see their names – ending in “mab” – in TV ads for treating everything from skin conditions to cancer.

As more monoclonal antibody (mAb) therapies are developed (1 in 3 new drugs are monoclonal antibodies1) and as patent exclusivity expires, these treatments are becoming more widely available. As a result, people are becoming increasingly interested in understanding this class of drugs being prescribed for themselves or people they care about.

What exactly are mAb drugs and how do they work? Read on to learn about monoclonal antibodies and why they’re so important in healthcare.

What are antibodies?

To understand monoclonal antibody drugs, it’s necessary to first know a little about how antibodies work in the body’s immune system.

The immune system protects the body from harmful substances, microbes and abnormal cells that can cause diseases. It’s a large, complex, and interconnected network of organs, cells, and proteins that work together to protect the body from illness. When the immune system recognizes foreign invaders, such as bacteria, viruses, or cancer cells, it makes proteins called antibodies to neutralize or destroy them without harming healthy tissue.

Anything that triggers an immune response is called an antigen. Antigens are usually structures on the outside of the disease-causing agent. When an antibody recognizes and attaches to an antigen, it serves as a flag to attract disease-fighting molecules or as a trigger that promotes cell destruction by other immune system processes.

Pharmaceutical researchers have taken advantage of the disease-fighting power of the body’s immune system to produce monoclonal antibodies that mimic what natural antibodies do but tend to work faster with more immediate results.

What is a monoclonal antibody?

A monoclonal antibody is a protein made in a laboratory to recognize and attach to a specific antigen on a disease-causing agent (e.g., a type of bacteria, virus, cancer cell, etc.). “Monoclonal” refers to the fact that all the antibodies are exact copies (clones) of a single antibody protein and are designed to recognize and bind to only one specific antigen.

Monoclonal antibodies are used in scientific and medical research as well as for the diagnosis and treatment of diseases, including different kinds of cancers, inflammatory and autoimmune disorders, infections, and nervous system disorders. FDA-approved mAb treatments have been available since the late 1980s.

Monoclonal antibody drugs have proven to be more successful at treating certain diseases, such as some cancers, than other types of treatments. Because they are tailored to recognize only one specific antigen, monoclonal antibodies are more precise than other treatments, improving their effectiveness and reducing some side effects.

In most cases, monoclonal antibody treatments are administered as an intravenous (IV) solution or as an injection. They can be given as therapy by themselves or with another drug.

How do monoclonal antibody drugs work?

Monoclonal antibodies can be designed to work in different ways. In some cases, a single monoclonal antibody may even work in multiple ways. The following are a few examples.

Some monoclonal antibodies attack disease-causing cells directly. When the antibody attaches to the cell, it triggers a series of events that causes the cell to self-destruct.

Monoclonal antibodies can serve as a flag to make it easier for other immune system cells to find and destroy the disease-causing cells.

In the case of some cancers, monoclonal antibodies can block the connection between a cancer cell and proteins that promote cell growth or prevent the growth of blood vessels needed for cancer cells to survive.

Because of a monoclonal antibody's ability to recognize and connect to a cancer cell, it can serve as a delivery vehicle for other treatments, such as chemotherapy and radiation. This approach can reduce damage to healthy cells because the monoclonal antibody transports the treatment directly to the target cancer cells.

Some drugs combine two monoclonal antibodies, one that attaches to a cancer cell and one that attaches to a specific immune system cell. This connection can promote the immune system to attack the cancer cells.

Why are monoclonal antibodies important?

It would be hard to overstate how much monoclonal antibodies have transformed healthcare. They are the basis for treating conditions ranging from cancer to high cholesterol, allergies to osteoporosis, migraines to cardiovascular disease. Monoclonal antibodies are also essential for typing tissues for organ transplants and blood transfusions.

Their precise targeting and high level of sensitivity make monoclonal antibodies versatile tools for basic research and diagnostics, in addition to their therapeutic applications. They are used to investigate the pathways of numerous diseases, including cancer, Alzheimer’s disease and autoimmune disorders.

Beyond their clinical applications, monoclonal antibodies are important components of in-home testing kits for determining ovulation, pregnancy, and other conditions. They are used by government agencies to monitor infectious agents like HIV and influenza, as well as salmonella and other bacteria that cause food poisoning.

Safeguarding mAb drug quality

Because they are biological molecules made using biological processes, monoclonal antibodies are subject to minor variations from one production lot to the next, however, consistent quality is important for their use as therapeutics and diagnostics. Manufacturers conduct rigorous testing of critical quality attributes throughout monoclonal antibody development and manufacturing processes to demonstrate product safety and effectiveness.

One primary quality consideration is the control of potential contamination. Process-related contaminants can include DNA or protein from the host cells used to produce the monoclonal antibodies, components of the materials used to grow the cells, and microbial contaminants from other sources. Product-related contaminants can include size variants (aggregates and fragments) and other structural abnormalities.

Monoclonal antibody drug manufacturers use agreed-upon methods to measure critical quality characteristics and reference materials, such as those made by the U.S. Pharmacopeia (USP), to serve as a benchmark to verify that their analytical systems and methods are working as they should be. Standard-setting organizations like USP work with manufacturers and regulators to develop standards and reference materials to address some of the most urgent quality challenges associated with mAb drug manufacturing.

mAb drug availability

mAb-based therapeutics are becoming more widely available for several reasons. Scientific and technical advances have made it possible to now make monoclonal antibodies in large quantities at relatively low cost. Another use of standards and reference materials is to verify that quality is maintained even as manufacturing processes are changing. As some of the monoclonal antibody drugs currently on the market reach the end of their patent exclusivity periods, biosimilar versions will likely be introduced (biosimilars are biologic medications with no clinically meaningful differences from the original). Many more monoclonal antibody drugs are in development, undergoing clinical trials, or awaiting regulatory review and approval.

This expanded access to monoclonal antibody drugs offers hope to millions of people suffering from acute, chronic, and sometimes life-threatening conditions. Knowing that manufacturers and regulators are using proven methods and reference standards and materials to safeguard the quality of these products lets healthcare providers and patients use them with confidence.