Biological Response Modifiers

By Malcolm Weir, DVM, MSc, MPH; Rania Gollakner, BS, DVM, MPH

What are biological response modifiers?

Biological response modifiers (BRMs), also called biological therapeutics or biotherapeutics, are naturally occurring substances that modulate the immune system by directly stimulating, directly suppressing, or indirectly affecting it. Broad examples of BRMs include antibody therapies, immune signaling proteins, and cancer vaccines.

How do biological response modifiers work?

Each BRM works in a different way. Some act as an immune system stimulant, meaning they increase the immune system’s natural responses. These stimulants can be used to increase and “aim” the pet’s immune system at a virus or cancer cells.

Other BRMs act as an immune system suppressant, meaning they decrease the immune system’s response. These suppressants can be used to treat diseases that are caused by an overactive immune response, such as atopic dermatitis (skin allergies) or inflammatory bowel disease (IBD).

Lastly, some BRMs affect the immune system indirectly by working on the disease itself or on another body system.

What are some specific examples of biological response modifiers?

Interferons: These are naturally occurring proteins that can be reproduced in a laboratory and administered to patients as a treatment. Some interferons can activate immune system cells to fight cancer or infection, or directly target cancer cells or viral/bacterial/parasitic behavior. Other interferons are used to treat diseases by altering the way the immune system responds.

Interleukins: These are naturally occurring proteins that can be reproduced in a laboratory and administered to patients as a treatment. Some can increase the immune system response by promoting growth or production of immune cells; this can be useful when treating infections or cancer. Some can decrease the immune system response by suppressing the growth or production of immune cells, which is useful in treating immune-mediated diseases.

Colony-stimulating factors: These are naturally occurring proteins that can be reproduced in a laboratory and administered to patients as a treatment. They increase the growth, production, and function of red blood cells, white blood cells, and platelets. This can be useful when blood cells are depleted during cancer treatment or in cases of severe infection.

Monoclonal antibodies: These are proteins that are produced in a laboratory and are modeled after naturally occurring proteins. They are administered to patients as a treatment for infectious pathogens or cancers. Antibodies target and attach to specific markers (antigens) on the pathogen or cancer cell; once attached, these antibodies signal the immune system to destroy that cell. Antibodies can be created and administered to specifically target and destroy only the problem cells, leaving healthy, normal cells untouched.

Monoclonal antibody therapy has also been used to treat canine atopic dermatitis or atopy (Lokivetmab or Cytopoint®). The antibody identifies and stops a specific itch-signaling molecule (Interleukin 31) from reaching the brain, and thereby provides relief from the itchiness of atopy. Other monoclonal antibody therapies have been developed to treat the pain of degenerative osteoarthritis in both dogs (bedinvetmab or Librella®) and cats (frunevetmab or Solensia®).

Vaccine therapy: Vaccines are produced in a laboratory and are composed of antigens (specific markers) from the cancer or infectious agent being treated. These vaccines teach the immune system how to recognize and destroy the cancer or infectious cells, either as a prevention before disease occurs, or as a treatment after a cancer develops.

When are biological response modifiers used?

BRMs are used most often for immune-mediated diseases, cancers, certain types of infections, and chronic skin and joint problems. Examples of these conditions include the following: atopy (skin allergies), fibrosarcoma, feline leukemia, feline immunodeficiency virus, immune-mediated hemolytic anemia/thrombocytopenia, lymphoma, osteoarthritis, or pemphigus. Often, BRMs are less toxic than drugs previously used to treat cancers and immune-mediated diseases, so they may also be used in cases where other treatments are not feasible.

Will my pet need to stay in hospital for this treatment?

Most BRMs do not require an extended stay in hospital after use; however, BRMs should be administered under direct veterinary supervision. Your veterinarian may also recommend observation in hospital on the day of administration to monitor for adverse effects.

What are the side effects / adverse effects of BRMs?

Side effects vary depending on the BRM used and may or may not occur. Generally, side effects of BRMs may include skin lesions, fever, nausea, vomiting, appetite loss, tiredness, muscle soreness, or allergic reactions.

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