What Are Antibodies? 

Antibodies, also known as immunoglobulins (Ig), are natural proteins that defend the body against foreign proteins, commonly referred to as antigens. There are five types of Ig, with IgG being the most common. They are made by a specific type of white blood cell called B lymphocytes. Although IgG recognizes many different types of antigens, each IgG molecule recognizes only one very specific antigen. This antigen may be present on an invading microorganism, a toxin, or a host protein, such as a cancer cell or a protein that causes pain. When IgG recognizes its antigen, it attaches to it, and the IgG-antigen complex is destroyed, which removes the antigen.    

What Are Monoclonal Antibodies?

Monoclonal antibodies (mAbs) are laboratory-made IgG. A single B cell is designed to make only one (“mono”) specific IgG antibody that recognizes a very specific antigen. This cell is cloned (“clonal”) so large amounts of the same antibody are made. The first monoclonal antibody (mAb) was produced using mouse B cells. However, the mouse IgG was foreign to the target species and caused allergic reactions. A safer monoclonal antibody (mAb) was created by replacing some of the mouse IgG with the target species' IgG. This was referred to as a “chimera”.  

The manufacturer must demonstrate that the mAb drug is both safe and effective when used to treat the indicated disease in the target species. The variety of diseases treated with mAb is broad. For example, mAb can target: 

• A foreign protein on microorganisms such as bacteria, fungi, or viruses.
• Toxins in the blood.
• An abnormal protein in the body, such as in cancer cells.
• A weakened immune system, making it stronger, or calming an overactive immune system that may cause autoimmune diseases.  
• A single overabundant protein that, for example, worsens pain or inflammation.
• Specific cells for the delivery of drugs or radioactivity that help with diagnosing and treating certain diseases.

Monoclonal Antibodies Are Very Different from “Small Chemical” Drugs 

Small chemical drugs are medications with a low molecular weight, composed of chemicals combined in a laboratory. Two advantages of mAb cause them to be much different than small chemical drugs: they are very specific, and they are very large (often 500 times larger than most drugs). Some important examples of differences between mAb and smaller, chemical drugs include:

• Only tissues that have the target antigen will be affected by the mAb. Chemical drugs can affect every cell in the body, causing effects even in normal tissues. 
• Monoclonal antibodies must be administered by injection, either directly into the vein or subcutaneously (under the skin). If given orally, the body will digest the mAb just like any other protein.  
• Proper handling and storage are very important to a healthy mAb. They can be destroyed by excessive cold, heat, or sunlight. When damaged, mAb will not work because it cannot recognize the target protein.
• Unlike most other drugs, mAb should only be used in the target species for which it is approved. This is because the target antigen may differ among the species. More importantly, an mAb designed for one species (such as a dog) is a foreign protein in another species (such as a cat). This will cause the cat’s body to destroy the dog mAb, potentially triggering an allergic reaction.
• Most chemical drugs are removed by the liver or kidneys, but mAbs are removed by the cells that have their target antigen or by cells lining blood vessels. This results in several differences:
  • Many chemical drugs may cause liver and kidney disease, but this is unlikely for mAb.
  • Many chemical drugs must be used carefully or not at all in patients with kidney or liver disease. This is generally not a problem for mAb drugs.
  • The kidney and liver are common sites for chemical drug interactions, but not for monoclonal antibodies (mAbs). In fact, most chemical drugs can be used in patients that are also receiving mAb.
  • Removal of mAb by cells is much slower. Because of this, mAbs are usually given only once or twice a month.

Adverse Reactions to Monoclonal Antibodies

Although safer than many other drugs, mAbs are not without risk. Because they are foreign proteins, some patients may develop an allergy to mAb. This is rare. However, allergies may show up with the first dose or may not show up until after several doses. Another, more common adverse reaction occurs when the target protein that causes disease in one organ is important in another organ.

For example, nerve growth factor is a protein that causes pain in patients with osteoarthritis, and it may also play a role in repairing certain damaged tissues. Other adverse events may have little to do with what protein is targeted by the mAb. The Food and Drug Administration monitors adverse reactions to mAb drugs. It is important to report any adverse reactions to your veterinarian that occur after your pet has received treatment with a mAb. If you are unsure whether your pet is experiencing a reaction to the drug, discuss this with your veterinarian.

Current mAb Approved for Use in Dogs and Cats 

Monoclonal antibodies will change how some diseases are treated. They are often safer and possibly more effective than chemical drugs. While many human mAbs have been approved, only a handful of animal mAbs have been approved. These include:

• Parvovirus mAb, which targets a protein found in the canine parvovirus. It is administered only once, directly into the vein, as early as possible when your dog is sick.
• Several animal mAbs target antigens that worsen pain or inflammation. Usually, these drugs must be given for several months.  
  • Two mAb drugs that target nerve growth factor (a protein that worsens pain associated with osteoarthritis) have been approved for use in animals: bedinvetmab (Librela®) for dogs and frunevetmab (Solensia®) for cats. 
  • Interleukin-31 (IL-31) is a protein that worsens itching in dogs with atopic dermatitis. It can be treated with Lokivetmab (Cytopoint™).
• Cancer is a common indication for mAb use in humans. However, currently, only one drug is approved for use to treat cancer in dogs. Gilvetmab mAb works by exposing certain tumor cells that are hiding from host immune cells, which can then destroy them.