Might There Be New Ways To Treat Feline Lymphoma In The Future?
Ron Hines DVM PhD
Janus Kinase Inhibitors = Jakinibs
I originally wrote this article in 2017. At the time I was more optimistic that a Jansen‘s drug, Ibrutinib (Imbruvica®) might offer some hope to cats with the slow intestinal form of lymphoma. Perhaps more than the treatments veterinarians had available at the time. Imbruvica® is a jakinib, a new class of drugs that interrupt specific internal cell processes. The drug is still highly regarded as a first-line treatment for several forms of lymphoma in humans. (read here)
Unfortunately, it turned out that it wasn’t a cure and it wasn’t selective as to which lymphocytes it destroyed – it kills the non-cancerous lymphocytes as well as the cancerous ones. Nether you or your cat can live without lymphocytes. Consequently, the incidence of side effects in human lymphoma patients is substantial: lung and respiratory infections, skin infections, bleeding, diarrhea, oral ulcers, nausea and vomiting. Many chemo drugs can be used to kill lymphocytes. But none of them can distinguish between a normal lymphocyte required to maintain a health immune system and lymphocytes that have formed a cancerous subgroup. A Chinese company, Dizal Pharma, markets a similar jakinib, DZD8586, as a lymphoma treatment for humans. No publications mention either of them ever having been used to treat cats.
More successful medications to treat intestinal and other lymphomas in cats will have to await scientists locating compounds in the cancerous lymphocytes that healthy non-cancerous lymphocytes do not contain (or contain in larger or smaller amounts than the normal lymphocytes). Cells do not become cancerous without a change occurring in their DNA. (read here) It will be scientists searching for human lymphoma cures who will make those discoveries, not veterinarians. We ride on their coat tails.
Monoclonal Antibodies or mAbs
Once scientist know what has physically changed in lymphoma lymphocytes, we will be well on our way to selectively destroy them. Then a whole new class of drugs becomes possible cures. They are the monoclonal antibodies (mAbs) – custom designed antibodies that scour the body searching for a specific compound to destroy. (read here) The only mAbs available to veterinarians now are Cytopoint®, an MaB marketed by Zoetis for allergic itching in dogs and Solensia® (frunevetmab), a mAb marketed to control arthritis pain in cats. (read here) Neither have any application in treating lymphoma in cats. Besides, mAbs must be specifically tailored to the tissue of the species to which they are intended to be given. A product designed for humans will not work in cats or dogs. If attempted, the pet’s immune system will quickly reject and destroy the mAb.
A MaB medication that has become popular in human medicine for treating lymphomas is rituximab. It attacks a particular protein (CD20) found on the surface of lymphoma cells. It is found on your cat’s cancerous lymphoma cells too. However like all mAbs, rituximab is only accepted by the species it was designed for – humans. So it would have to be altered in the same way the Solensia® MaB was modified by Zoetis before it could be given to cats. Rituximab is also unable to distinguish between cancerous lymphocytes and non-cancerous lymphocytes, so it destroys all of them. That can lead to reactivation of dormant viruses, anemia, diarrhea and vomiting. Another of these engineered anti-CD20 monoclonal antibodies is Ibritumomab. It suffers from the same deficiencies.
There might be a second path once we learn how to tell a cancerous lymphocyte from a healthy one. That involves a technique called CAR-T – a method of reprogramming the body’s immune system to seek out and destroy cells with certain specific characteristics. It is a complicated, time-consuming and expensive process. The CAR-T procedure is effective in monkeys, laboratory mice and rats, and dogs. (read here) But I know of no research on its use in cats. Perhaps veterinary school scientists will attempt to. There is certainly a pressing need for such a project.
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