Dr. LeBlanc: I love the idea of the next generation of researchers because there's always going to be so much demand for answering these questions because there's absolutely no shortage of questions. So maybe the first piece of advice is don't be afraid to ask questions.
Don't be afraid to say, well, why? Why do you do it that way? Or why can't we do this that I see other groups doing it? Why can't we profile cancers the way that they do in physician oncology? What kind of barriers exist and why are they there and are they things that we can work together to overcome?
Dr. Venable: Welcome to the Veterinary Cancer Pioneers Podcast, the show where we delve into the groundbreaking work of veterinary professionals who are dedicated to advancing the field of veterinary oncology. I'm your host, Dr. Rachel Venable, and I'm thrilled to embark on this journey with you.
Dr. Venable: I'm your host, Dr. Rachel Venable, and today I'm thrilled to introduce you all to Dr. Amy LeBlanc. Dr. LeBlanc is a board-certified veterinary oncologist, and she's also a Senior Scientist and director of the CCR Comparative Oncology Program at the National Cancer Institute NIH. In this position, she directly oversees and manages the comparative oncology trials consortium which designs and executes clinical trials on new therapies and tumor-pairing pet dogs. So very exciting. I definitely want to hear more about that. It's a very unique and very cool position. Dr. LeBlanc was also an associate professor with tenure and director of translational research at the University of Tennessee, College of Veterinary Medicine. Her group was one of the first to publish on molecular imaging and PET CTs in dogs and cats. And she's given numerous lectures on companion animals and imaging and translational research, as well as drug and imaging agent development. So has really been involved in a lot of exciting, really interesting things. So without further ado, please join me in extending a warm welcome to Dr. Amy LeBlanc. Thank you again so much for being here.
Dr. LeBlanc: Oh, it's my pleasure. Thank you, Dr. Venable, for the invitation. I'm excited to share thoughts, ideas, and just all the information I can with you and your listeners today.
Dr. Venable: Well, thank you. Your position, to me, it seems very unique. I don't know very many vets, and maybe you can educate me on that, how many other veterinarians you work with, but I just think at the NIH and if you can tell us a little bit more, you know, kind of what does that role look like? What's your day-to-day? Because I think it's probably just so different from what most of us veterinarians do.
Dr. LeBlanc: My team and I are at the National Institutes of Health and we're in the National Cancer Institute. All of our work really has a mission towards ending and reducing the burden of cancer on the human public, but my job is to really look at that through the lens of the naturally occurring cancers that affect our companion species, our cats and dogs, and other species share our lives and households and what we can learn from them that can actually benefit everyone with an emphasis on improving human cancer outcomes. So we have a focus mostly in dogs for a lot of different reasons. I think they're a species that we know a lot about. They're already a very important part of biomedical research. So most of our work has to do with studying cancers that affect dogs, and we study the biology of those cancers. We also work with a consortium of veterinary schools throughout the U.S. and Canada to do, as you pointed out, clinical trials for the purposes of identifying new and exciting ways to treat cancer.
And when we do that, we not only help humans, but we also help the dogs that participate in the trial themselves, their families, and other dogs like them now and in the future. So that is what I do on a day to day. A lot of it is administrative and in the lab and working with my colleagues in my program, but also through other investigators at the NCI. And also a lot of time spent working with collaborators out in the community. So veterinarian teams that are at veterinary schools or at medical schools that are interested in working with us to sort of advance that agenda at their own institution. So lots of time, I think maybe spent on the phone or now on a conferencing platform like this.
Dr. Venable: Technology's fun, it kind of changes it up, right?
Dr. LeBlanc: It does, for sure, yes. And our days are sort of spent thinking about where our program's going, our mission, our goals, but also spending a lot of time thinking about the open clinical trials that we have, so we have several that are open right now, and then also planning for future trials that will open in the next, you know, sort of six to 12 months, and working on ideas in the lab that also have mostly these days of focus and in osteosarcoma, which is the disease that we have really in most of our scientific focus centered on that disease.
Dr. Venable: It is such a fascinating disease. And I think, you know, as veterinary oncologists, we're all pretty aware how dogs, sadly, it's a very common cancer. But in people, it's quite rare. And also very sadly, it's usually pediatric, right? It's a younger person's disease. And that also seems to be a community that's really open to clinical trials, probably because they just, however, we can move the needle and improve things. And it has been really fascinating that relationship over the years of how dogs have really been able to help kids. Have you really seen that with just the trials and what you guys have moving forward?
Dr. LeBlanc: Yeah, I mean, I think osteosarcoma is definitely sort of the best example of where a canine disease very closely mirrors a pediatric adolescent, young adult human disease. One of the other diseases that we're learning more and more about that sort of has that theme are gliomas, which are a really rare and devastating brain cancer. When you look at them from the standpoint of molecular profiling, they actually mimic more closely pediatric glioma than adult human glioma. Maybe that's emblematic of how we continue just to learn and ask questions, and now that we have a lot better profiling tools, better reagents, better laboratory assay capabilities, better computational tools, better molecular profiling tools, and really just a much better knowledge of the canine cancer genome. We are now able to ask those kinds of questions. Whereas maybe 10 years ago, we were really sort of handcuffed and not able to ask as sophisticated as questions that we can ask now. So the more we learn, the more we realize that we can't necessarily assume what population of humans matches, and it may really surprise you, you know, I think when we look deeper, we think, “Oh, well, I had no idea that a canine glioma would really, you know, affecting an adult or geriatric dog would look molecularly much more like a childhood tumor.” So, yeah, I think that that's a really interesting facet of what we are learning.
Dr. Venable: Yeah, it's really interesting. And it is interesting how much we're learning about genomics and genetics with cancer and profiling because my understanding, they do that a lot in human cancers, is that correct?
Dr. LeBlanc: Yeah, I mean, I think that these days when you have a diagnosis of cancer on the physician oncology side, molecular profiling has become very common. I think it's quite rare actually these days to not have that be a part of your workup, especially if you're a patient that's being cared for at a major cancer center. And so I think what we would like to see happen is for canine patients for that to take hold as well. And there are certainly groups of folks from the research side and the development side that are looking at ways to implement that and incorporate those tools into the patient management strategy for dogs.
And when that happens, we really start to realize more and more the similarities that exist between human and canine cancer from a molecular standpoint. And it gets really exciting when you realize that you can pick up a lot of the same mutations and alterations in genes and look at expression profiles and, you know, the interplay between tumor cells and the immune system. You start to get more and more echoes of commonality between dogs and humans, which for us is just super exciting.
Dr. Venable: I agree. It is really exciting because, you know, when you look at a dog, you wouldn't think we necessarily have that much in common, right? But we really do. It's amazing to me how we can genetically have so much in common, right? Like you were saying, looking at that level of things, and it's still common. That's fascinating to me.
The other thing, and I'm curious if you get this sometimes too, Dr. Bergman was saying, especially in the beginning, when he tried to talk to people about using the dog as a good model to study cancer, people were thinking that we were giving dogs cancer, you know, versus like they do a mouse, but no, they actually just get cancer at a pretty high rate. Do you run into that with some of the researchers and physicians?
Dr. LeBlanc: I used to. So I've been in my current position here at the NIH for it'll be 10 years in July. I used to get that initially when I would come in and give talks to groups of people who had really not much if any exposure to veterinary medicine. So maybe they were groups of scientists that really didn't own a pet or have experiences with pets in the household, hadn't really met anyone like me before. So they had literally no idea that this was happening. And not just that it was happening, but that the diseases that we observe as veterinarians have really strong clinical, molecular and histologic links to what is seen in humans. So these days, it's rare for me to get in front of an audience and ask that question, you know, who knows about dogs, getting cancer, most everyone raises their hand now. So I think I have Dr. Bergman and others in the community to really thank for that because that doesn't really happen all that often anymore, thankfully.
Dr. Venable: Good. And you guys are even moving the needle more for people like me, like coming in and getting excited about this stuff. So that's awesome. Glad to hear, glad to hear that we're moving that needle. You know, you mentioned clinical trials. Is it a big part? You talked a lot about universities. Are these pretty much only at universities that you guys do NIH-level studies or are there any private practices that you guys work with?
Dr. LeBlanc: We currently are only working with a veterinary school network that operates at universities. And some of that has to do with the types of studies that we do. They require some equipment and infrastructure that you wouldn't necessarily have at a private practice like a minus 80 freezer or a sterile hood or refrigerated centrifuge, like some things that you will really only find at a university. And they take a lot of our patient visits for these trials, take a lot of time. And that's always a real challenge and a busy referral practice, which is not to say that university clinics are quite busy. I think we've certainly observed across the board that pet owning public is very much aware of what's available for their pets with cancer.
So I think most veterinary oncologists find themselves with a fairly full waiting room these days. So, you know, our intent, you know, we are certainly not the only group that's doing clinical trials and dogs and cats with cancer, but we have sort of chosen to stay within our little, you know, sort of niche of partners and it works well for us. So that's kind of where we live right now. And as of today, we have 19 members throughout the US and Canada. And that really affords us a nice geographic spread of case recruitment across the country. And in Canada as well, we have two Canadian sites. We have currently four open trials. So it's a good feeling to be that busy.
Dr. Venable: Oh, that's great. And what does it take to become an NIH site? I mean, I know you mentioned some of the specific equipment that, yes, I would say I've never worked at a private practice that had those, a refrigerated centrifuge. That's new to me.
Dr. LeBlanc: So our members in the university setting, you know, there's a list of membership criteria, they have to have the requisite number of faculty members across the specialty of oncology, but also the affiliated surgery and internal medicine, pathology, radiology, etc. And they need to have a clinical trial staff that's dedicated and able to act upon sort of a complicated protocol with lots of study visits and lots of data management and things like that.
And the types of studies we We run, you know, people always ask, "Are they big studies? Are they small studies? Are they long or short?" And really the answer is that our studies are very fit for purpose. So we focus a lot on the types of questions that are being asked.
So the questions that are being asked scientifically really drive the choice of the patient population and the way the study is going to be designed, and what types of tumors or conditions are we interested in, and really what are the goals, right? What are you hoping to learn from the trial? And so some studies are as small as 18, 20, 25 dogs. And some of our larger osteosarcoma studies had, you know, 300 plus dogs in there. So it really just, I think depends on the type of question that you're trying to get at.
Dr. Venable: Sounds like you've got a lot of puzzle pieces to put together. Do you like puzzles? Is that something that?
Dr. LeBlanc: Oh, I love puzzles. I think during COVID, that was like one of the things that my family, I have two teenage daughters, and my husband, the four of us, we did a lot of puzzles during COVID. You know, I just, I think I sort of have that unfettered curiosity about me. I like asking why, why, why, why? Like, why is this like this? Why can't we do that? Or why don't we understand this particular problem?
And if we don't understand it or don't really have a feel for why it's happening, then how can we get to a place of better understanding? And I think if I've learned anything about being here at the NIH, which is certainly, you know, where you find the world's experts and sort of everything all in one place, which is super exciting and really challenges you, I think, as a scientist and as a clinician to grow when you're surrounded by that level of expertise.
It's forced me to also just up my game a little bit to know and ask questions that maybe weren't asked in my prior life as a clinician and also have the ability to answer some of those questions, you really can't treat a disease that you don't understand. And that's where I think our emphasis is right now. It’s trying to just really get a better understanding of the diseases we see every day. Because if we can understand them better, then what ultimately will follow will be more tailored, more effective therapies.
Dr. Venable: Oh, that makes a lot of sense. You know, instead of just this kind of shotgun approach, right, really understanding what you're doing to begin with. Now, when you were looking at that, is it something where you really, you know, do you guys kind of focus on the mouse and then work up to the dog and then the person or is it more circular? How would you say that works?
Dr. LeBlanc: So I think if you looked at what we're doing sort of lately, it's very iterative. So we sort of bounce back and forth quite a bit. I think that a lot of folks looking from the outside in think it's very linear, right? So you start with cells and then you move to a mouse and then you go to dogs and you go to people. In truth, that's not really how our group tends to think about it. These days, we're actually starting with data. So data that has been generated from real tumors, from canine or human patients. And we look at that data and we think about it in terms of patterns of gene expression, for example, or patterns in mutations or chromosomal abnormalities. And we like to make comparisons. So this is what the dog looks like. This is what the human looks like. Okay, so let's try to get a better understanding of that landscape. And then we think, well, do those changes in that data, that genomic data mostly, do they tell us anything about targets that are druggable. So does that data tell us, hey, you know, maybe you could try this type of therapy. And that's when we go back usually to cells. So we have cell lines, a nice catalog of cell lines from canine and human patients with osteosarcoma. And we say, well, if we have some drug targets in mind, and we have cell lines that recapitulate some of the facets of molecular changes that we see from those tumors. Can we design some experiments that take those drugs and see can we kill those cells in a dish? If we can kill them in a dish, then we feel good about being able to then make some mouse models to see if we really can kill the tumors 'cause killing them in a dish is pretty simple. Killing them when they're growing inside a mouse is a little harder. And then we just sort of build our confidence up about the approach and then we take that sort of approach and then think about tailoring it to a dog study.
And so we sort of circularly is probably a good way to describe it, but oftentimes we bounce back and forth too. So if we're seeing something that we don't expect based on the data, if we have an unexpected finding in the cell lines or in the mouse model, sometimes we have to go back to the data and say, Did we miss something or did we think about it in a different way? We bounced back and forth a lot between data and cells and mice. And then moving confidently, I think, into a dog study is important because dog studies are a lot of work. They're expensive. You're asking a pet owning family to commit to a trial. So you really want to be sure you're designing a trial that has all the right questions and data underpinning it because it is a pretty big endeavor.
Dr. Venable: Yeah, it all sounds like it can get really interesting, but really complicated quite quickly. Would you say that that is some of them the most challenges, especially even with just with comparative medicine trying to kind of get that, okay, this should make sense on paper. So why aren't we seeing it? Is that maybe one of the more challenges you run into with this?
Dr. LeBlanc: Oh, for sure. And I think that, you know, most of my colleagues in cancer, drug research research and development efforts would agree with me that these pieces don't always fit together perfectly. And sometimes you know why, you go back and you think, oh, well, okay, I chose the wrong cell line to test, or I didn't look at the correct mouse model, 'cause there's tons and tons and tons of ways to model disease and mice, and there's no just one way to do that. So it is frustrating and challenging, but sometimes you find things that you don't expect. And then it turns out to be a good challenge, not necessarily a negative challenge. But having said all that, I mean, I think dogs represent a really nice piece of a very complicated puzzle. They're not going to solve all of our problems when it comes to figuring out a better way to treat and manage cancer patients. But there's certainly, I think, a very valuable bridge between mice and human, that's how we see it at least. And I think that's a way that when we explain it to people, they're like, well, that makes a lot of sense.
Dr. Venable: But even just thinking about, you know, a mouse where you grow the tumor on their back per se versus a dog that developed it naturally, I mean, it does, it makes sense how, okay, this would be a more challenging, more real world, right? Similar to like what a person gets. And what have you seen so far, you know, and maybe this is too early to say, but have you noticed like, oh, if it does well in the dog trials, it's looking better in human trials, would you say, or are you not seeing that so far?
Dr. LeBlanc: I mean, we've definitely got lots of examples from the community. Here's a good example. We did a published study now looking at a small molecule that targeted a pathway in cells that's related to the way that proteins are handled, the way that proteins are shuttled in and out of different parts of the cell and the company that we were working with, and this is actually an NCI-sponsored study where we partnered with NCI and this small biotech company in our program, the three of us worked together on this study. And they said, you know, this is a really new and mostly unexplored way of treating cancer. We think it's got value. We have this data in cells and in mouse models, and we're really interested in exploring more details about how this drug works in dogs with cancer and we said perfect that's what we do. And because of the way the drug would target protein metabolism really for lack of a better way to describe it, it's kind of complicated but had to do a lot with protein management inside cells. We thought, well, there might be a good chance that this drug might be very good for a disease called multiple myeloma.
So as you know, multiple myeloma is a disease of B-cells, and B-cells are a part of your immune system. And their main job is to crank out immunoglobulin, which is a protein that helps you as a part of your immune system. So we thought, well, if these cells are highly dependent, and their main job is to make lots of proteins, maybe they'd be really sensitive to this drug. And it turns out we were right. And when we did the work and the dogs that had a lot of different types of cancers, but we also had a separate cohort of multiple myeloma patients, we saw a really nice efficacy signal with this drug. And that really was transformational for the company because then they were able to enter into some licensing and other legal agreements to move the drug forward for myeloma treatment in humans based on our canine data.
And that is exactly the kind of story that we like to think about because it really catalyzed the enthusiasm around the drug that not only was it well tolerated and it worked, it also opened up the confidence to go into a very specific form of cancer in humans that was really highly associated with the mechanism of how that drug worked. So it all just beautifully lined up and we were like, "Yay!”, you know, that's exactly the kind the thing we like to do. Does it always go that way? No. But in this case, it's a good example of where we feel like we can really help optimize that path.
Dr. Venable: That's great. And what would you say you look at in companies coming to you? Because I would assume you probably get, you know, I mean, NIH. I can imagine you guys get a lot of requests or different companies' emails I can only imagine.
Dr. LeBlanc: Yeah. I mean, it's why I think the biggest thing that we always think about right off the bat is, and this was a lesson that was taught to me by the Comparative Oncology Program's founder, Dr. Chand Khanna. So Chand always said, who's waiting for the data? Who is the stakeholder? Who will benefit from your work on their drug and what will happen next? So genie in a bottle, poof, the data is there. What will happen? The lesson there is you don't just do a study to do it. You do it because you're convinced that when you receive the data and the data is interpretable, it's going to mean something. It's going to satisfy an unanswered question or help someone get through a go-no-go decision point in the path of that agent.
And maybe your job is to kill a drug and keep it from going any further because it's not really got what it takes. And maybe that's just as valuable or maybe more valuable than helping move a drug forward in the example like I just gave you. So I think that that's probably where we spend most of our time thinking about the potential opportunities to work with folks that come to us with really interesting concepts. I think the second thing right next to that is, “Are we confident we can design a canine study that will result in interpretable data?” And when I say that, I mean, we don't do studies just to say, let's just see if this drug works. Let's just see if we get some responses. That's not good enough. We need to have a really good understanding of how all of the clinical data is going to be interpreted, and that we'll be able to say something about tolerability, exposure of the drug at the tumor tissue level, so relationships between like pharmacokinetics and pharmacodynamics, being able to like link drug dosing, drug exposure and target modulation, that sort of magic triangle. We really wanna be confident, we know what we're doing. And we wanna be able to create a data package that's interpretable, and that will be meaningful.
That's not always easy to do. I think especially when you get drugs that are going to maybe target molecule or a way that's not really well characterized in dogs, you know, how do you design a study? If you're not really confident that biology, that's so important to how that drug is thought to work. If it hasn't been credentialed in the dog, then it's going to be really difficult for me to design a trial with the right sort of testing and assays and support of it to know if the drug doesn't work, we need to know why. We definitely need to know if it works why it worked but maybe as important as if it didn't work we need to understand why it didn't work.
That's where a lot of trial concepts get weeded out because either the drug it's just too new it's too sort of unique or too early or it's just not compatible with dogs for whatever reason or the scientific questions just haven't been fleshed out enough. And we are a small group of people so we can't take every concept. But luckily, there are so many people out in the veterinary oncology community that are interested in doing this kind of work that even if we can't take the concept into our portfolio, there's plenty of other groups for people to work with that may have really unique or singular expertise that really fits well with that concept.
And so part of my job too is to make sure that the rest of the community, if I can't help a group that comes to me asking for help that I can connect them, hopefully to somebody who can. So I think that that's also, you know, part of our mission as a program is to keep the communications, you know, alive and well throughout the community.
Dr. Venable: I think you said a lot of great things in there, so much about what is the point of doing the study? Like you said, it's not just to see if it works. A lot of people don't understand, even, you know, as like vet students and things, when you start looking at veterinary studies, they don't realize some of that data, you can't really interpret. Like you're saying, like, I know sometimes, especially when I have specific cases and I look through the literature and I'm like, okay, so what happened? Then I'm like, the more I tease through it, and that's when I realized like, well, wait a minute, this is kind of apples and oranges. Like they were doing the best they could in a sense, cause it's hard to get enough dogs together. But then you realize you're like, wait, this started with saying like 30 dogs. But now that it's teased down, there's like three high grade. Like I do like what you're saying about trying to make sure if we're going to do it, that we've really thought it through doing good science.
I also really liked how you mentioned about negative results because I think that's something that's become more acceptable to publish negative results, right? Because like you said, if it doesn't work, you need to know why. What do you think about that? you know, just the more publications allowing negative studies.
Dr. LeBlanc: Oh yeah, I mean, I think that access to data, and maybe this is a good time to sort of talk about the Integrated Canine Data Commons. Access to data is really so, so important when it's made publicly available, which is really, I think, part of our mission because we exist on the back of the American taxpayer. Really important for us to make sure that when we generate data, that we share it with the community because that really belongs to all of us. All of the work that we do is a community resource. And so negative results are still results. There's still data. There's no telling who that's going to be valuable to. For example, like, you know, if you did a drug study and you generated pharmacokinetic data and you realized while the pharmacokinetic data indicate that we didn't dose the dog correctly, meaning we didn't give it enough or we gave too much or whatever. That pharmacokinetic data in dogs, even though it might have not helped you in your study, it might help someone else. Because somebody might someday be looking for a dataset from pet dogs that received drug X and they may not ever see it if the publication or the data doesn't get disseminated publicly. So that, I guess that that's another lesson I've learned is that all data is important. It may have been negative to you in terms of the question you were asking or trying to ask an answer, but that doesn't mean it doesn't have value. It's just could be viewed through a very different lens by a different group of people, a different scientific question. So we're really excited about the fact that the NCI set up a data commons like that, that is so specifically dedicated to housing canine data because it really didn't exist before. People had a way of sharing data publicly like GEO or other sort of forward-facing public repositories for all types of different data sets, but it wasn't canine. There wasn't just like one place you could go and say, I'm really interested in canine data. Let me find that. It's an exciting time for data sharing, I think, for everyone.
Dr. Venable: And what all is in that in the Integrated Canine Data Commons? I mean, do you have actual tissue or like if someone wanted If someone wanted to run blood samples, what exactly do you have when you say the data, if you can explain that some more?
Dr. LeBlanc: Most of it's genomic data. It's going to be sequence data, transcriptional or RNA sequencing or DNA sequencing data. There's some pharmacokinetic data in there. There's scanned H&E images of tumors. There's links to MRI data from a very large brain tumor set that we put in there a few years back. So most of it just to be clear is genomics. So if you, for example, were like, I'm interested in the transcriptional profiles of canine bladder cancer, you could easily go in there and find, and not just find the data, but the data commons environment that NCI set up actually has web-based tools that can help you analyze that data. So for people who are really just trying to get their feet wet in that comparative space. This is not just a place for data to be deposited, but it's also a place for you to have access to tools that will help you interpret and analyze it. So it's very cool that way. It's not just one thing. It can be quite a helpful research tool for people in general.
Dr. Venable: How do you access that?
Dr. LeBlanc: So there's a website that if you just literally typed in your search engine canine genomic cancer, you would find it. I can provide that for you in the chat or however you would like me to send that to you, but pretty easy to find. I think it's usually gonna be at the top of your screen.
Dr. Venable: That's awesome.
Dr. LeBlanc: Yeah, that does sound exciting. And it is interesting, like if you're thinking of a study design or study model, it sounds like that could be a good place to kind of dive in and just see like, you know, does this make sense? Does it not? 'Cause sometimes it is hard when you're just searching, whether it's PubMed or even Google Scholar. Sometimes it's hard to find, you know, especially the stuff you're talking about, because that's very specific.
Dr. LeBlanc: Yeah. And I think that the data management team that the NCI has put together to help make the Integrated Canine Data Common successful really spends a lot of time very carefully trying to understand what the data is. And there's a nice study description and a description of the types of canine patients that are linked to that data. So you can find even very granular details. Like if you just wanted back to the bladder cancer example, if you said I just want bladder cancers from boxers, you could see if that exists. If you were very interested in the specific breed of dog or if you were interested in osteosarcomas from Labrador Retrievers, you could query the K &I data commons, and it would tell you, well, we have data from X number of Labrador Retrievers with appendicular osteosarcoma. So it's really great that way, because every day that goes by, there's more and more data being put in there. And I think it's fifth year now. So it's growing and growing, and it's just really nice to see that.
Dr. Venable: How are people able to contribute research? Is that just from the different studies you guys are doing, or are there other groups that are literally, you know, kind of helping to dump things in for a lack of better word.
Dr. LeBlanc: Absolutely, I mean, we actually spend some time looking through the literature and finding data sets from published literature that we thought would be a great addition to the integrated K &I data commons.
And we reached out to the corresponding authors and said, “Hey, would you work with us on putting your data here? Maybe you had it in GEO or some other public repository, but can we lift it or link it somehow to our data commons?”
So it would be visible, more visible to somebody who might be looking for canine genomics data or other types of canine specific cancer information. So we actually spent some time a few years ago really thinking like what are the types of data that we feel have a lot of impact from the scientific literature. Let's go get it and bring it in here. And I think the words out because they that project team is currently got a queue of data sets that they are bringing in. A lot of careful QA /QC goes into that so that the end user, when they get access to the data, it's clean, organized, and very easy to use.
Dr. Venable: Yeah, that is really exciting. That's awesome. Yeah, I'll definitely have to look into that. And kind of thinking, you know, here is saying about how there's GEO, there's other groups that are more human-related, the Cancer Moonshot Initiative. You know, that's something that came out a few years ago really about trying the grants and things to get these projects see, you know, trying to cure cancer, right? We're trying to move the needle. So how are you involved with the Cancer Moonshot? Or are you involved?
Dr. LeBlanc: I guess I'm peripherally involved because part of what Cancer Moonshot money has made it possible for canine immunotherapy grants to be made available through the Precinct, a canine immunotherapy network. So Precinct was an iteration of collaborative U01 awards that were made available. I think the first iteration was in 2018, and then the second iteration was in 2022. And these are clinical trials conducted in dogs for the sheer and focused purpose of looking at immunotherapies that could be tested in dogs that would have value for human patients. So really, for the first time that the NCI released a very specific funding opportunity for dogs with cancer, which is not to say that there aren't other NIH-funded researchers who have achieved funding for canine studies through other R01 or U01 or program project grant opportunities because they have. That's certainly been happening for years, but this was really the first time that it was specifically stated as this is a canine immunotherapy granting mechanism. So that is really exciting. And I have worked on some committees and opinion groups to sort of say, well, this is how that RFA should be structured. And here are the types of things that could be asked and answered within trial concepts.
So I was asked to sort of educate program officers on what the landscape looked like, what types of canine cancers exist, and where they had good correlates with human cancer. And so it's just super gratifying to see the funding follow the interest, because I think a lot of people are interested, like, wow, dogs get cancer, but now there's actual multi-million dollar funding opportunities that help really get at the questions and really exemplify how dogs can be so valuable in that process. And I think especially for immunotherapy, right, because dogs have that intact educated immune system. They share the home environment with us, and you really can't recapitulate that kind of an immune landscape in a mouse model, especially one that's been modified genetically or otherwise manipulated or compromised, that's really difficult, if not impossible to do in mouse models. So dogs again really fill that gap, I think, especially in the immunotherapy space.
Dr. Venable: It is really interesting to think about, right, how they live with us, the microbiome, I mean, hearing more about that, and that seems to be so much about your environment.
Dr. LeBlanc: They're sleeping on your couch in your bed and eating your food. Eating your food. They're going on walks with you. Maybe they're coming to work with you. I mean, they really have that singular exposure there that really adds dimensionality to them, and the types of cancers they get are probably a reflection of that.
Dr. Venable: Right, right. Yeah, I know that is, that's really interesting. And I love all this new, you know, how can we can learn from dogs and new studies and I like how you guys are thinking through some of those studies, and that's really interesting. And what advice would you give to, you know, an aspiring veterinarian or veterinary oncologist that's interested in comparative oncology.
Dr. LeBlanc: I love the idea of the next generation of researchers because there's always going to be so much demand for answering these questions because there's absolutely no shortage of questions. So maybe the first piece of advice is don't be afraid to ask questions. Don't be afraid to say, well, why? Why do you do it that way? Or why can't we do this that I see other, you know, groups doing it? Why can't we profile cancers the way that they do in physician oncology? What kind of barriers exist and why are they there, and are they things that we can work together to overcome? because certainly there's no end in sight to that battle we have with cancer. We are making incremental progress, but we certainly aren't where we want to be in the treatment of both dogs or cats or humans. All of us still have unmet needs for our patients.
And I think that continuing to educate yourself is really important. I mean, I came here after having already a 10-year academic career, And I had to sort of start at the beginning and really learn a whole new vocabulary and really get more familiar with very sophisticated tools and data sets in the way and a language really that didn't really exist in my prior position.
And so when you immerse yourself in really such a rich scientific community, it forces you to keep learning. Don't be afraid to up your game. And lifelong learning and questioning is always going to be something that aspiring researchers, the successful people, I think, around me that I learn from every day, that's what I have seen them do. And I like the idea of maybe emulating that unending thirst for information. It's really important.
Dr. Venable: I love that. Yeah, asking questions, keep learning, keep asking questions. I think, yeah, what are the biggest failures? It's just failing to try, right? So like you're saying, just ask and go see what you can find.
Dr. LeBlanc: Yeah, I mean, I think a lot of us, the questions that we ask and try to answer are born out of frustration. So, I mean, how many times have you sat in front of a pet owner and said, I don't have anything else to offer you? Or we've tried everything that we know to try, and nothing is working. Like that frustration that all of us feel, and I'm sure that our physician counterparts feel that same way when they are in front of a patient that's not responding, you know, the way that they all had hoped that person would that frustration can be turned into power if you really harness it and use it for good. And there are countless people around me who, you know, work on really tough rare diseases, and you just get fueled by those stories and that, and you hear from the patients themselves that they're grateful for everything that you're trying to do for them. And the more that you talk to people in the community and you change ideas, I think it can help keep your spirits up when you get frustrated, but that's what we all need right is to connect with others in the community to help us move forward.
Dr. Venable: So true, and I love how you said turning frustration into power. That's awesome. I like that. I might have to I might have to steal that.
Dr. LeBlanc: Oh, take it.
Dr. Venable: I'll quote you.
Dr. Venable: Also any exciting breakthroughs that you're anticipating in the next few years, whether comparative oncology, people, veterinary, anything that looks interesting coming down the pipeline?
Dr. LeBlanc: So I guess there's probably two things to mention. One of them is an osteosarcoma initiative we've had in the lab now for a couple years. Simply put, it's called dog squared. It's decoding the osteosarcoma genome of the dog. Pretty self-explanatory. What we're trying to do is, As I mentioned earlier, get a better understanding of the disease because if we can understand the disease, we will have a much better shot at actually treating it appropriately. So what we're doing with, again, starting with dogs is doing a lot of different characterization experiments on the tumor tissue we harvested from the large osteosarcoma clinical trials we've done recently.
So whole genome and whole exome and RNA transcriptional profiling and sequencing, looking at the histologic images of the tumors themselves under the microscope and using AI to extract patterns that may not be visible to a human eye, linking all of those types of data to outcomes of those patients so we can identify new ways to predict outcomes and then seeing if those methods, those algorithms are transferable to human. That initiative that is ongoing in the lab has given us some pretty exciting discoveries that we've found that in the immune landscape around canine tumors, you can generate a transcriptional profile that predicts outcome that is very closely linked to the types of immune cells that traffic in and around these tumors, and that that same transcriptional signature will predict outcome in people.
Now we're looking at gene copy number and gene dose relationships to ask questions about whether the amplification or loss of certain genes might also have predictive power for both dogs and people. So we're really knee-deep in a lot of that work. That's a really exciting time for us because I think all of us would say, well, you know, osteosarcoma in dogs and osteosarcomas in humans, they look a lot alike. But now we're sort of like getting into the weeds. Like, okay, well, we want to know specifically about the genes and the transcription and the expression of those genes and really getting into more of that biology. So that's an exciting time for us right now.
I guess the other exciting thing for us is that we opened a new clinical trial just last month working with another NCI investigator, Dr. John Schiller. So Dr. Schiller and his team created Gardasil, which is the human HPV vaccine. And they in their lab have worked very closely on a concept that simply put says, if you can create an antiviral immunity through vaccines, can you then redirect that immunity against cancer? So essentially what you're doing is making it look like a tumor is infected with a viral disease. And then, the patient's own antiviral immunity can be used, can be redirected toward the tumor cells themselves. So we have an open clinical trial, it's a two-arm trial. One arm uses the Gardasil vaccine along with Shingrix, which is the vaccine for shingles. So varicella roster. We combine the Gardasil and Shingrix vaccines and we vaccinate dogs with these human vaccines and help dogs with cancer create this antiviral immunity. And then they have a tumor. We inject proteins into the tumor by intratumoral injection to make it look like the tumor is infected with HPV and the varicella chickenpox, essentially, viruses. And so you then create this immunity and then you redirect the immunity.
And we have the other arm of that study is using the rabies vaccine. So dogs already have a really nice rabies titer typically, and they have a robust level of rabies immunity because they've been required to be vaccinated for rabies in this country, yearly or every three years. So if we inject rabies proteins into the tumor cells, we can redirect the anti-rabies vaccine immunity and vaccine-induced immunity toward the tumor. So we just opened that trial last month, and we are super excited about it. Because vaccines are so safe and widely available, it would be an approach that if it works, the way that it works in mice really, really well, if it works in dogs, then it would potentially be something that could be deployed in low resource settings, which is I think something we always need to be aware of, that not everybody lives in a place where you can just receive really high-level cutting edge care for your cancer. Sometimes you are living in a part of the world where you don't have access to those resources, and a low-resource setting approach to cancer therapy that could be widely deployed with very cost-effective measures, we'd be able to help a whole lot more people and potentially a whole lot more dogs too. So that's really, you know, very new and very exciting opportunity for us. And we were so, so grateful for Dr. Schiller to reach out to us and say, I think you guys are doing something cool, and I'd like to get in on it. So that's what we did. And that, so that study is open at five US universities currently and is open and enrolling. So stay tuned.
Dr. Venable: Oh Yeah, that all sounds really exciting. Very interesting. I really like that. And I think the public loves immunotherapy. I think everyone likes the idea if you don't have to give chemotherapy. And like you said, you know, if it doesn't have to require the same kind of handling that chemotherapy and radiopharmaceutical type stuff needs, then, you know, your general practitioner in rural areas could do it.
Dr. LeBlanc: Yeah, I mean, because vaccines are just such a part of our life now and they're so safe and widely available and cost-effective ways of preventing disease that it's a really neat idea to think of them as actually a cancer therapy. So we're excited to see where that work will take us, and we should have the results of that trial later on this year.
Dr. Venable: Right, oh, that's really exciting. Well, awesome, well, as we're getting ready to wrap this up, you know, this has been just fascinating. I'm so glad I got to chat with you about all of this, just learned so much. But as we're getting ready to wrap up, is there someone that you would recommend that would be a good fit for this podcast?
Dr. LeBlanc: You should talk to Dr. John Schiller. He is a huge fan of our work and has now turned into a huge fan of dogs. You talk about somebody who in his career, because of the success and the implementation of Gardasil as a vaccine strategy, he and his team have saved thousands of lives. I'm confident of it. So he might be one to talk to and some other really exciting people to talk to in the vein of immunotherapy, the pioneers, right? In that sense, Steve Dow, Nikki Mason, Cheryl London, if you haven't talked to those folks, highly, highly recommend them as well.
Dr. Venable: Yeah, I know those are great people. And yeah, that the vaccines, like you mentioned, yeah, I probably saved so many lives, so really very exciting stuff. I'll be excited to see what we learn from dogs with it.
Dr. LeBlanc: 2024 is going to be a big year for us, so stay tuned.
Dr. Venable: Well, that's it for this episode of the Veterinary Cancer Pioneers podcast. If you enjoyed this episode and gained valuable insight, we would be so grateful if you could share our podcast with your friends and colleagues. And it would be even more wonderful if you want to give us a five-star rating, positive review, or any kind of feedback on Apple Podcasts or wherever you listen. The Veterinary Cancer Pioneers Podcast is presented to you by ImpriMed.