MD Anderson Cancer Center
Lisa Garvin: Welcome to Cancel Newsline, a podcast series from the University of Texas, MD Anderson Cancer Center. Cancer Newsline helps you stay current with the news on cancer research, diagnosis, treatment, and prevention providing the latest information on reducing your family's cancer risk. I'm your host Lisa Garvin. Today, our guest is Dr. Laurence Cooper. He's a Professor of Pediatrics here at MD Anderson and we're going to be talking about increasing collaborations between doctors, oncologists, and veterinarians. Now Dr. Cooper I guess this is kind of new - the fact that human doctors are reaching across the aisle to veterinarians. What is the basis for that?
Dr. Laurence Cooper: Yeah, thank you. It's new and it's old at the same time. These ideas around what's called comparative oncology where you're comparing oncology in other words cancer between one species and, and another, have been around with us for a long time and most of your audience will recognize that a lot of cancer therapies were explored in the mouse model, and indeed, we have these highly engineered mouse strains that over decades of work have actually helped us understand the biology of human cancer. What we recognize, and our colleagues at Texas A&M Medical, Texas A&M University, I should say the veterinary college at, at Texas A&M recognized that their cancers that occur in animals, outbred animals might look a lot like the cancers that occur in humans and maybe we could actually learn together about how to take care of if in some ways your pet dog, and if we do that, we could also learn how to take care of pet humans or real humans.
Lisa Garvin: Because I think that pet owners have come to recognize that their animals do get some of the same diseases including cancer as they do.
Dr. Laurence Cooper: Yeah you're quite right, and in fact, more and more we understand that there are similarities between the cancers that occur in our companion animals, our dogs, for instance, and also that occur in humans and we understand that at a very deep level and indeed we understand the genetic basis in many cases for the types of cancers that occur across species. So again, this idea of comparative oncology where one can learn by comparing cancer types between different animals actually add essentially to the knowledge so that we can actually do a better job taking care of not only humans but quite frankly dogs with cancer.
Lisa Garvin: And from what I understand the sequencing of the canine genome a few years back was a big step forward in this field.
Dr. Laurence Cooper: It's been a big step forward indeed and that was a seminal event, but so too has been there's also this understanding that the types of medicines that veterinary oncologists are using share a lot of similarities for the types of medicine that human oncologists are dispensing. So there're several touch points. There's this idea that canine or veterinary oncology we have a lot of the molecular tools or genetic tools available, and at the same time, we also have a lot of the similar protocols available. So when those, that, that, those two events as well as some other platform experiences come together, they really develop a common language and from that common language we can talk to the veterinary oncologists and they can talk to us, and as a result, we can start to ask questions about can we essentially cure a dog, can we cure a human, and if we can't, what are the difficulties, what are the challenges.
Lisa Garvin: So basically, the animals that we would benefit most from collaborating would be dogs, cats, pigs and horses or?
Dr. Laurence Cooper: Yeah, I mean I, I think the experience we have is with the companion canine with your pet dog really because those owners that are certainly that go to Texas A&M University are self-motivated to essentially help their, their dog.
Lisa Garvin: So is cancer a prevalent disease in dogs?
Dr. Laurence Cooper: Yes, very much so. Each year about a million pet dogs develop cancer of some type and one of the most common types of cancers is lymphoma, and in fact that lymphoma looks very similar to human cancer. So Texas A&M they see probably around 500 or so cases of canine lymphoma each year and those owners that take their dogs to the Texas A&M are very motivated to have their dogs treated. Not, not all owners choose quite frankly to have their dogs treated if they have lymphoma, but, but for those families with a pet dog that did have this type of diagnosis and reach out to the veterinary oncology community, they receive treatments and chemotherapy that's very much like a human would and we recognize that in partnership with a veterinary oncologist there called Heather Wilson and she's terrific. And she essentially dispenses four drugs, the same four drugs essentially that are given to humans obviously adjusted for canine size. But when we were working together and thinking through this problem, it occurred to us at MD Anderson that we actually give a fifth drug and that's an antibody, an antibody called Rituxan, which is essentially a commercial grade reagent that binds a molecule called CD20. So why is that important? Well, many lymphomas when they arise from malignant B cells express CD20 on the surface. So if you give these four chemotherapy drugs sort of the workhorse drugs plus the fifth antibody those... that package essentially comes together and you get a much better chance of remission. Well in the canine world, they don't have an antibody to CD20, so essentially they're limited to just the four drugs and they have an inferior survival. So even though they see many, many cases of B cell lymphoma at Texas A&M, the chances of actually having a deep cure are pretty remote. So while many dogs will go into remission, about, only about 20% of those dogs will have a sustained survival as a result of giving the chemotherapy, so they're handicapped. They need an additional help, they need an additional immunotherapy.
Lisa Garvin: Dr. Cooper you're doing some research or developing canine T cells. Can you tell us about that?
Dr. Laurence Cooper: Yeah and that was actually right. So what we, we do in the human world if you would is generate T cells for human application, so T cells are a type of naturally occurring immune cells, cell that floats around your body, nests in your bone marrow, grows in your lymph nodes, and is responsible for keeping you safe both from perspective of infections but also from cancer. So, for instance, if people are immunosuppressed, they have a much higher chance of developing a malignancy. So we've been generating T cells, what's called ex vivo, outside of the body and propagating or growing, culturing these T cells so that they can be not only swell in number, but actually be programmed to have increased potency, a greater bang for the buck, if you would. So we've understood that human T cells grown in this manner might have a therapeutic potential, might be able to exert an antitumor effect if infused into a human. So what we were thinking of is if the canine with cancer only gets four drugs and can't get, if you would, the, the B cell antibody, maybe instead of an antibody, which in all intents and purposes is a type of immunotherapy, we could swap out essentially the antibody in the canine experience for canine T cells and put them back in, in the context of their chemotherapy, so it's a win-win. So the way it's a win for the dog of course is that they get their four drugs and now they get their T cells added back. And in that context, we can begin to learn across many, many dogs how that type of therapy works. It's a win for the humans because we're growing the T cells for the dogs exactly and I do mean exactly the same way that we grow the T cells for humans. So if there is biology in the dogs that looks favorable, we can swing around and say okay if it's working in the dogs, let's do a trial on humans and see if it works there too.
Lisa Garvin: Now as far as tracking cancer in dogs, is there such a thing as like a serotype database or any kind of morbidity and mortality information or tumor registries for dogs?
Dr. Laurence Cooper: There are. In fact, there are a lot of data in terms of what dogs develop cancer over time, and in fact, breeders know a lot of this information. Let's say if you buy certain breeds of dogs you might know they have hip dysplasia those types of things, well similarly, other types of dogs like Golden Retrievers actually get a lot of lymphoma. So there are those types of genetic data and prevalence data if you would that allow the veterinary community to know the risk profiles for the various breeds. But I think on top of that there's been this understanding that dogs have been domesticated for the past 15,000 years, so basically speaking for the last 15,000 years, dogs and humans have lived together eating the same food, sharing the same environment, you know, if it's like my dogs, they share the same bed and so they're really a part of our family.
Lisa Garvin: And they have kind of some of those same lifestyle factors.
Dr. Laurence Cooper: They have exactly right, they have the same lifestyle factors. So as a result, they have the types of cancers that are reminiscent to the human experience because they're sharing our environment. So if immunotherapy works in the dog in what's called an outbred model, really in an example of a dog that is for all intents and purposes with respect to this type of biology sharing a lot of 'human' characteristics, then if the immunotherapy works in that environment, it has a much greater chance of working when we actually apply it in humans. So our general sense of it is that instead of using the mouse model, which is excellent for many pieces of biology, but for this particular application, we thought going to the canine would be much more informative and the owners like it because they get this new therapy, and in fact, if you look at the trial data and it's all now published and so it's all online, it actually worked. These T cells actually did have an anti-tumor effect. They were able to control the cancer in the canine and we can learn from that experience and do the same types of trials and we actually have a trial now, in fact we have multiple trials now open to humans where patients at MD Anderson are being enrolled on studies to receive T cells in the, in essentially in combination with their standard of care therapy.
Lisa Garvin: So I guess I want to make clear for everybody that we're not experimenting on people's pets, we're just taking advantage of treatment that's already been done.
Dr. Laurence Cooper: That's a, that's a great question and it's really, we're really sensitive to that question. So the owners of the pets are given a consenting form just like any patient, any human patient on a clinical trial. So the owners are taught and educated about the therapy and they have a complete permission to say no and there's no demerit because they know they still get their standard of care chemotherapy, their four drug, if you would, chemotherapy for lymphoma. But if they say yes, then we spend a lot of time educating them and we release a product that's manufactured actually here in Houston at MD Anderson Cancer Center and transported to College Station and that product meets the same testing requirements as if it was going into a human, so we take this very seriously, and in fact, there is very little funding for this so we actually have to raise money and generate a lot of additional resources to raise the bar if you would. But the owners because they essentially speak for the animals, speak for their pet dog or actually would advocate for the animal and say yes or no and that's not the case in many other biology experiments in when we do trials if you would on mice, we have to have a second type of authority typically speaking it's the Animal Welfare Community and the veterinary, veterinarians who work here at MD Anderson who make sure that we do a good job with respect to our mouse colonies. When we work with the pet dogs, we're working directly with the owner, so of course they have their pet animals' interests at their heart, and in many cases, these owners really find this not only fascinating, but then go above and beyond, and we have really many, many examples where these dogs have gone back to their local communities because Texas A&M is a major referral center, so these dogs will go back and then our team here at Anderson will ship little boxes of blood collection tubes and these owners on their own dime will go down to their local veterinary practice, get the blood drawn on the dog and ship the blood back to us so that we can understand and do a better job in terms of understanding the biology, for instance, how many T cells are in the dog? Where did the T cells go? These donors could keep a diary for us so we actually understand the side effects and so all of this is very motivating on both sides of the fence both for the owners, and also, for the researchers here at MD Anderson.
Lisa Garvin: Now where do we go from here? I mean obviously in humans we're looking for genetic mutations, we're looking for tumor markers, and, and various cell receptors. Where do you see research going on the veterinary side?
Dr. Laurence Cooper: Yeah we, we, we have a lot of plans actually. The, the, the trial was so successful that we continue to get referrals from patients, and if you would, their owners and in fact those referrals have been worldwide. We actually have a dog that's a Seeing Eye dog, a beloved dog in the Netherlands that's been shipped to us for the purposes of getting its T cells infused. So that trial continues and we will continue to enroll canines on a kind of a case by case basis and it is somewhat expensive for us to tell you the truth, so we have to be a bit careful in terms of managing our, our funding. But the energy is also turning to answer some big questions in immunotherapy or T cell therapy. For instance, we want to do a better job understanding where the T cells go and we can do that by scanning the dog using magnetic resonance imaging or MRI and partnering with a company we've developed a tracer that can be loaded into the T cells while they're being made in the laboratory and then when the T cells are in the body, in the canine, they'll sweep around the blood system, nest into the cancer cells, and amongst the cancer cells and when asked the question, 'Can we see those cancer cells on the, excuse me, can we see the infused T cells on the MRI Imaging?' And that would be a very important question because then we can say you know how well did the T cells get there, how long did the T cells get there, etc. So that's a big time question. Additionally, we want to make a better T cell. We want to make a T cell that actually packs an even bigger punch so that we can arm the T cell so that when it binds the cancer cell, it will do so in a way that, that cancer cell has, will be damaged to a greater effect. And for that, we've actually gone back now, if you remember the CD20 molecule I was speaking about, we've actually engineered the T cells to recognize that canine CD20 molecule, so it's, while there's no Rituxan or CD20 antibody for the dog, we can now make a CD20 specific T cell which in all intents and purposes has the binding property of Rituxan and the killer function of the T cell and the two together might have some real biology in the, in the dog and then can of course be applied in the humans.
Lisa Garvin: Obviously we're focusing a lot on dogs, but are there other companion animals or animals like pigs or horses, which are kind of similar that you would see research being done in those areas?
Dr. Laurence Cooper: Yeah I think this world of comparative oncology really can be expanded beyond the pet dog. Cats, for instance, would be an interesting pet animal to help. They get leukemias, as we all know. Similarly, horses, for instance, get melanomas the grey mares get melanomas standing out there in the sun in the Texas heat. Pigs again can get cancers. And we've done a little bit of work on this. We understand that we can grow, for instance, swine T cells just the same way that we can grow canine T cells, we haven't yet practiced in the, in the cats. But to tell you the truth you know these, this type of biology, this type of comparison between one species and another is so rich and so exciting to be able to learn how biology works in one species and comparing it to another that a lot of these experiments and a lot of these trials should be done. But like many things, it's a question of resources, and that's really, you know, one of the big issues in the, you know, we all understand the need to do better. So one way to help us understand how we can cure cancers is whether we can cure cancers in these companion animals and for that we need support, we need help, and we need people to write to their Congress people and, and, and essentially fund comparative oncology and fund the NIH.
Lisa Garvin: Because both man and beast will benefit.
Dr. Laurence Cooper: Exactly right.
Lisa Garvin: Thank you very much Dr. Cooper. If you have questions about anything you've heard today on Cancer Newsline, contact ask MD Anderson at 1877-MDA-6789 or online at mdanderson.org/ask. Thank you for listening to this episode of Cancer Newsline. Tune in for the next podcast in our series.
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