Hoping to extend survival rates in cancer patients, researchers at MD Anderson Cancer Center in Houston, Texas, are conducting trials on companion dogs with lymphoma in a partnership with veterinary oncologists at Texas A&M University College of Veterinary Medicine, College Station, Texas. ONA recently spoke with Laurence Cooper, MD, PhD, professor and section chief, Cell Therapy, Children’s Cancer Hospital, The University of Texas MD Anderson Cancer Center, about the research program.
ONA Why did you undertake working with dogs in your research on lymphoma?
Cooper Human biology drives this change. We have reached a point of diminishing returns with our current animal models, especially mice. We can learn a lot about the immune system from mice and apply that to humans. But in terms of engineering immune cells for therapy, making cells in the laboratory for transplantation into humans, using a mouse animal model to predict for both therapeutic and toxicity effects in humans is difficult. We needed a model that was better akin to the human condition, and for that we turned to the dog.
Dogs and humans have been living together for at least 15,000 years, and we share many of the same things. We share environments … sometimes we share the same food. When examining cancers, canine cancers are very much like human cancers. Cancers in a highly specialized mouse environment very often are not representative of human biology; whereas in a dog, they are. Similar to human cancers, canine cancers occur spontaneously, are heterogeneous in their makeup, and are a major challenge to treat.
ONA How was this project initiated?
Cooper We started by talking to our veterinary oncologist colleagues at Texas A&M University, who explained that cancer develops spontaneously in approximately one million dogs each year. A large number of those cancers are lymphomas. I realized that this could be a win-win situation. We have a therapy for humans that we want to learn more about, and they have canine patients that need therapy. I thought we might be able to do something together, and help people and dogs at the same time.
We realized this would not work for everybody, but it would probably work for a subset of motivated dog owners. We found we could bring the dogs’ T-cells to the same level of integrity that we use for humans. We created an informed consent for the dog owners to read and sign, so they understood what the program entails. This therapy is currently administered at no cost to the dog owners, because we were able to generate sufficient funding for the trial so that we can administer the T-cell treatments to the dogs.
The strength of the research is that the same principles and technologies used to make human T-cells are used for making canine T-cells: the same manufacturing platform, the same agents, the same recipe book. Part of the reason for using dogs is that not many reagents are available for dogs, but these tools are compatible in both humans and dogs. But more importantly, everything we learn from the dog can be directly applied to the human. We knew that if we made the T-cells in exactly the same way, then we should see the same kind of effect in humans that we see in dogs. And we did not see any toxicity in the dogs.
ONA Were there any unusual findings in the dogs?
Cooper One of the nice things about the dog model is that the dogs went home at night. We never thought about doing that for our human patients; we keep them in the hospital. The dogs teach us that this treatment is very well tolerated; they are just fine, at home playing and being part of the family as usual. We can learn so much from this model. This study just scratches the surface; it is the first of many we are conducting.
ONA If the dogs can go home at night, does it mean they are less sick than humans who undergo this treatment?
Cooper Not necessarily. We are very nervous during the early stages when conducting human trials. But now that we see how well the dogs respond, we are beginning to talk about using T-cell therapies in the outpatient setting.
ONA Is there a concern about contracting infections in the outpatient setting?
Cooper Well, that is a possibility; but the primary strategies for not contracting infections is to avoid anybody who is sick and make sure people wash their hands. Hospitals are great, but you can be safe at home too.
ONA How did the dog owners react to their dogs becoming research subjects?
Cooper We are fortunate in that we had wonderful families participating in the trial. They really got into it and helped us. I am a pediatric oncologist. I take care of kids with cancer. I have a busy day with a lot going on. From the perspective of running my program, I find it enormously helpful to have people around me who really want to participate in the research. Instead of my having to hire technicians to go down to mouse cages to observe and monitor the mice, I have all these families who are basically volunteers. They keep notes and email them to us. We are very fortunate to have this community. It may not be a scientific community, but it is an interested community.
We have learned that people really want to participate. Just because they are in the community and may not be scientists or trained does not mean they are not interested or capable. I believe we have a huge talent pool out there, whether it is for human or canine oncology.
ONA How did the dogs respond to the therapy?
Cooper They tolerated the T-cells very well. Although it wasn’t curative, unfortunately, the therapy really prolonged the amount of time the dogs had. We have two dogs that are still alive, which is remarkable because they really should not be.
ONA Where will you go from here?
Cooper We are figuring out what the next steps are. We talked to our Texas A&M colleagues about how to handle the volume of people who want this treatment for their dogs, and what we can do to provide this therapy without going broke. Because at the end of the day, we love our dogs, right? And we want to make sure that we are advancing care for humans.
This is comparative oncology. Although we have a grant from the American Kennel Club for this trial, it is a labor of love at this time. We have all these wonderful ideas, and there has never been a better time than now to explore these possibilities. There are so many things we can bring to the patient with cancer, but we depend on federal funding if we are going to make a difference. If we are going to cure cancer it is going to take everything—dogs, humans, everything we have. It is not going to be a one-shot deal. ONA
Bette Weinstein Kaplan is a medical writer based in Tenafly, New Jersey.
O’Connor CM, Sheppard S, Hartline CA, et al. Adoptive T-cell therapy improves treatment of canine non-Hodgkin lymphoma post chemotherapy. Sci Rep. 2012;2:249.