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An Urban Experience
Safety of Monoclonal Antibody Therapy
The side effects of biological therapy depend on the type of treatment and the target of the therapy. In people, side effects can include flu-like symptoms,
such as chills, fever, muscle aches, weakness, loss of appetite, nausea, vomiting, and diarrhea. Some patients develop a rash, and some bleed or bruise easily. All of these depend on the target of the mAb. The long-term side effects of the various currently available biological therapies will be better defined with future research from which will also surely emerge new and valuable forms
of these treatments. This compares with traditional pharmaceuticals, which have a real risk for safety due
to overdose; concomitant drug interactions; underlying conditions; or contraindications, such as species or age.
An additional difference between traditional small molecule pharmaceuticals and mAbs is the way that they are metabolized and eliminated from the body. Small molecules are metabolized by the liver or intestines and eliminated by the kidneys or gastrointestinal tract. In contrast, mAbs are eventually eliminated via intracellular catabolism in the lysosome, where they are broken down into peptides or amino acids that can be either reused for synthesis of new proteins or renally excreted. Those mAbs in circulation that bind to the neonatal receptor on endothelial cells are protected from degradation such that they are recycled back into the plasma. This is part of the reason for their long half-life.
For all of these reasons, mAbs are relatively safe to use in treating people and animals with co-morbidities, such as liver disease; concurrently with many other pharmaceuticals; and in animals of any age.
How Are Monoclonal Antibodies (mAbs) Made?
To create mAbs, researchers inject mice with an antigen from a human or animal. They then harvest the antibody- producing cells from the mice and individually fuse them with a myeloma cell (cancerous B cell) to produce a fusion cell known as a hybridoma. Each hybridoma then divides to produce identical daughter cells or clones— hence the term “monoclonal”— and antibodies secreted by different clones are tested to identify the antibodies that bind most strongly to the antigen, have the longest half-life, etc. Large quantities of antibodies can be produced by these immortal hybridoma cells.
Because murine antibodies can themselves elicit an immune response in humans or other animals, which would reduce their effectiveness, the murine antibodies are often speciated (humanized, caninized, etc.) by replacing as much of the mouse portion of the antibody as possible with portions from the target species. This is done through genetic engineering (Figure 2).
Figure 2. Through genetic engineering, the murine antibodies that can actually elicit an immune response and reduce mAb effectiveness are speciated by replacing as much as possible with a portion from the target species (eg, canine).
Some mAbs stimulate an immune response that destroys cancer cells. Similar to the antibodies produced naturally by B cells, these mAbs “coat” the cancer cell surface, triggering its destruction by the immune system. US FDA-approved mAbs of this type include rituximab, which targets the CD20 antigen found on non-Hodgkin lymphoma cells, and alemtuzumab, which targets the CD52 antigen found on B-cell chronic lymphocytic leukemia (CLL) cells. Rituximab may also trigger cell death (apoptosis) directly.
Monoclonal Antibody Therapy in Veterinary Medicine
There are currently (as of November 2016) three monoclonal antibodies approved for use in veterinary medicine in the United States, and they are all licensed by the US Department of Agriculture (USDA) for use in dogs. Blontressâ targets CD20 on lymphocytes and aids in the treatment of dogs with B-cell lymphoma. Tactressâ targets CD52 on T lymphocytes and is indicated as
an aid in the treatment of dogs with T-cell lymphoma. Both of these products are manufactured by Aratana Therapeutics.
CytopointTM is a monoclonal antibody that reduces clinical signs of atopic dermatitis (AD) in dogs. It targets the circulating cytokine canine interleukin-31 (IL-31), which has been shown to be elevated in dogs with AD. IL-31 has been demonstrated to cause pruritus in dogs; and inhibition, both in laboratory dogs and client-owned dogs with atopic dermatitis, controls both pruritus and inflammation. Cytopoint is manufactured by Zoetis.
Nexvet Biopharma has completed and published information on two different monoclonal antibodies targeted at the inhibition of nerve growth factor
(NGF). These work by inhibiting NGF, which acts on pain-sensing nerve fibers to increase their excitability and increase the sprouting of new nerve fibers into inflamed tissues. NGF has been found to be elevated in the joints of dogs with osteoarthritis. Ranevetmab will be used to control pain associated with canine osteoarthritis. Frunevetmab is being developed as a monthly subcutaneous injectable for the control of pain associated with osteoarthritis in cats.

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