A few months ago I wrote an article describing a developing monoclonal antibody treatment option for treating B-cell lymphoma in dogs: (http://www.petmd.com/blogs/thedailyvet/jintile/2013/oct/new-treatment-for-dog-cancer-lymphoma-30979). Monoclonal antibody therapy represents a promising option for veterinary patients with a variety of tumors. This type of treatment capitalizes on the animal’s own immune system, using it to specifically target and attack cancer cells, while simultaneously affording a reduced risk of systemic side effects when compared to conventional chemotherapy drugs.
Since the time of publishing this article, a group of medical researchers in Vienna, Austria, have put forth the results of a small study describing a new and different monoclonal antibody for dogs. This antibody reacts with the canine version of a cell-surface protein called epithelial growth factor receptor (EGFR).
EGFR is mutated in many forms of cancers in both people and animals, and are most often found in epithelial cancers, which are tumors of the linings of different organs/tissues. Examples of epithelial tumors include mammary tumors, skin tumors, and lung tumors. Mutations in EGFR can lead to unregulated cell division and growth (e.g. formation of tumors) and can also help cancer cells figure out how to invade into other tissues and spread throughout the body (e.g. metastasize).
There are a variety of anti-EGFR monoclonal antibodies available for humans with cancer. One such “human” drug is called Cetuximab ®, which is structurally very similar to the newly developed canine anti-EGFR monoclonal antibody. Cetuximab ® is used to treat people with metastatic colorectal cancer, metastatic non-small cell lung cancer, and different forms of head and neck cancers.
Currently, veterinary patients with epithelial cancers (including those mentioned above treated with Cetuximab ®) have little treatment options beyond aggressive surgery and radiation therapy. Conventional injectable and/or oral chemotherapy protocols, though recommended, often lack evidence-based results to suggest their use substantially changes the outcome in pets.
Researchers showed the newly developed antibody was able to bind to the surface of canine cells overexpressing EGFR and that application of the antibody caused significant inhibition of canine tumor cell growth/proliferation. Moreover, the antibody was able to cause significant tumor cell killing via direct stimulation of other immune cells in petri dishes.
The next step will be establishing the safety and efficacy of the drug “in vivo”, meaning testing whether the results seen in the cells in the laboratory are translatable to live animals. This will usually entail safety trials, followed by efficacy trials, then potentially even larger-scale clinical trials. Each step requires a great deal of time and finances and compliance, which typically translates in to a long lag on knowing any further information while results of such studies are analyzed.
It’s interesting to note that while human oncologists have used monoclonal antibodies to treat many different cancers for over 20 years, this form of treatment is in it’s relatively infancy for veterinary oncologists.
This likely stems from 1) the astronomical costs associated with the development of such drugs and 2) the major limitations to the current manufacturing and purification processes necessary to mass-produce the antibodies. It’s not unusual for the costs associated with monoclonal antibody therapy to approach over $50,000 US dollars per year for individuals with cancers. In the veterinary world, this is simply not a realistic option.
This latter point is one of my main concerns for the when/if monoclonal antibody therapy becomes a potential option for veterinary patients. Whether discussing the previously described treatment for lymphoma or the potential new option for epithelial cancers, we have to consider what measures can be taken to ensure the treatments won’t become cost-prohibitive for owners? How can we ensure all our patients have access to the drugs? Will this even be possible, given what we know from our human oncology counterparts?
It’s also important to keep in mind that in people, drugs such as Cetuximab ® are usually used in conjunction with other forms of chemotherapy, rather than as a single-agent treatment. Therefore, monoclonal antibodies are unlikely to be a “magic bullet” for our patients. Veterinary oncologists will still recommend aggressive surgery, radiation therapy, and even injectable and/or oral chemotherapy, in combination with an immunotherapy option. Again, issues related to cost, owner concerns for their pet’s safety and quality of life, and other emotional factors will certainly come into play.
The take home message is progress is certainly being made in our field and exciting new options are likely to be available within the next few years. It can be frustrating to recognize how my profession lags behind the advancements afforded to my human physician counterparts, but as Frederick Douglass said, “If there is no struggle, there is no progress.”
When we consider that veterinary oncology is truly still in the infancy of existence, learning about these new options suggests to me that overall, we are doing a pretty good job of progressing despite our struggles – with patients who tend to be much more tolerant of our shortcomings, and a whole lot cuter as a whole.