Using Autologous T–Cells to Treat Canine Non-Hodgkins Lymphoma

From Decoded Science

While chemotherapy for canine lymphoma kills cancer cells, it also hinders the work of the dog’s own immune system.

Researchers at Texas A&M University and the University of Texas MD Anderson Cancer Center have found that t-cells, an important part of the immune system, taken from a dog before chemotherapy is begun, can be cultured to produce more t-cells and then returned to the blood stream after chemotherapy finishes.

The re-introduced t-cells can then help fight B-cell lymphoma.

Dr. Heather Wilson, Veterinary Oncologist in Small Animal Clinical Sciences Department at Texas A&M, told Decoded Science that the preliminary study yielded better results than expected.

She expressed optimism that the next stage, which will involve genetically altering the t-cells to make them more specific, could lead to even longer durable long-term remission.

And, given that the treatment has few, if any side effects, it offers an option for humans, particularly children, who may not be ableto tolerate chemotherapy’s toxic side effects.

Fighting Canine B–Cell Lymphoma With T–Cells: What’s Wrong With Standard Chemotherapy?

Lymphoma takes several forms, but diffuse, large b-cell lymphoma is the most common type. This form is also the most deadly, with a life expectancy of only three to four weeks if left untreated.

Unfortunately, even with treatment, dogs given standard chemotherapy often only experience one year of durable remission. Another problem is that a side effect of standard chemotherapy is an alteration in the balance between the two types of t–cells. Cytotoxic (cell killing) cells normally make up 90% of a dog’s t–cells, and the other 10% consist of helper cells. Dr. Wilson describes the helper cells as ‘generals’ directing the ‘foot soldier’ cytotoxic cells to go where needed. When this balance is reversed, as it is for cancer patients, there are too many generals and not enough foot soldiers.

Replacing Chemotherapy With T–Cell Therapy for Non-Hodgkin Lymphoma in Dogs

Dr. Wilson’s Texas A&M team, working with researchers from MD Anderson Cancer Center and Baylor University, have succeeded in selectively growing more cytotoxic t–cells and then infusing them back into their canine patients.

With the right balance of t–cells, the dogs’ own bodies were then better able attack the cancerous cells.

While this is great news, there are difficulties in culturing enough t–cells from each dog to complete the treatment.

This limits the number of times a dog can receive infusions, whether or not his t–cells are back to the correct proportion.

But the unexpected success of the initial trial, which was actually designed as a safety study, provides hope.

Canine Lymphoma Treatment: Next Phase

Not only is the team now focused on improving t–cell culturing, they are moving on to the next phase, genetically modifying the t–cells to make them more specifically programmed to attack b–cell lymphoma. The genetic modification should further improve durable remission times. Dog owners interested in helping with this research may be able to get involved in Texas A&M’s clinical trials. The Clinical Trials page on the university’s website explains which dogs are eligible to participate, and how to enroll in the trials.

While increasing long–term remission gives dogs more time, Dr. Wilson’s long–term goal is even more exciting. She told Decoded Science that she hopes eventually to see autologous cell therapy that will be effective enough to replace chemotherapy, so that dogs, and people, do not have to suffer from the significant side effects they presently face during treatment.

Resources:
O’Connor, C.M. et al. Adoptive t-cell therapy improves treatment of canine non–Hodgkin lymphoma post chemotherapy. (2012). Scientific. Reports. 2, 249; DOI:10.1038/srep00249. Accessed July 4, 2012.
Modiano, J. Non-Hodgkin Lymphoma. Modiano Lab at the University of Minnesota. Accessed July 4, 2012.