Dr. Mason: And of course, at that time, you know, that was sort of three years or so after checkpoints and CAR T-cells were just sort of voted the breakthrough of the year. And so immunotherapy was then and still is, of course, extremely hot. And it became very apparent in that initiative that we needed an additional model, if you like, or as again we like to say parallel patient population that really could help accelerate those types of therapies in the human space.
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.
Hello and welcome to the podcast. I am so excited today. I have Dr. Mason with us and really just even going through a brief version of her bio. There's so much to cover. She's a professor at the Department of Pathobiology at the University of Pennsylvania School of Veterinary Medicine.
She holds the esteemed Paul James and Charles Gilmore Endowed Chair Professorship. She has a veterinary degree from the University of London and a PhD in immunology from the University of Pennsylvania. Dr. Mason completed a postdoc fellowship at the Abramson Cancer Center. She's also a board-certified internist. She's leading the first canine cancer immunotherapy consortium backed by the Cancer Moonshot Initiative. Her research group has developed innovative immunotherapies for dogs with cancer, autoimmunity, and infectious diseases, so not just cancer. And her work in comparative medicine aims to expedite the clinical application of these therapies for both people and dogs. And some couple notable achievements that I feel like as oncologists, a lot of us were very familiar with the recombinant Listeria vaccine for dogs with osteosarcoma. She got the one health award for excellence for that.
She also recently received the International Canine Health Award from the Kennel Club in England in recognition of her ongoing work and achievements in improving canine health. And she recently made a fellow of the Royal College of Veterinary Surgeons. So she actively leads multi-institutional clinical trials and her lab specializes in evaluating and developing Carty cell therapies and making significant strides and adoptive immunotherapies. And her company, it's called Vetigenics, that she's part of. So we'll get into that as well. So much stuff to cover here. I'm so excited. And please help me and welcome Dr. Mason.
Dr. Mason: Thank you so much, Rachel. I'm so excited to be here. It's really a pleasure. So thank you for having me.
Dr. Venable: Oh, thank you. And, you know, as I mentioned, looking through your bio, you've done so much stuff. And I think something that's a little bit different than a lot of us in oncology is you've really gone into immunotherapy. And what made you so interested in that? I mean, you're also looking at infectious disease. You know, you don't just stop at cancer. So what made you so interested in immunotherapy?
Dr. Mason: I think it was really during my residency at Penn in internal medicine where I became interested in the immune system and mostly actually in autoimmunity and seeing a lot of patients with immune-mediated hemolytic anemia. And I couldn't really quite understand why dogs' immune systems got it wrong. You know, humans' immune systems get it wrong and start to attack your own tissues. So I sort of wanted to learn a bit more about that. And I was very frustrated with just giving high doses of cred or whatever immunosuppressive agent was trendy at the time, seeing, you know, many of those patients developed thromboembolic disease, partly because of the IMHA and my therapy. So I took the plunge and I was very fortunate enough to get a PhD place here at Penn in immunology.
And I learned a lot about basic immunology there. It was actually sort of in infectious disease, which I was a little less interested in. But I learned about the immune system. I learned about how the immune system is tolerized and shouldn't attack your own tissues. And then I learned about how things could go wrong and you can break tolerance and start to attack your own tissues. And then in my postdoc, I went to work with Carl June at the Abramson Cancer Center, where he was trying to do exactly that to break tolerance and try and get people's immune systems to attack their own tissues. But in these cases, their own tissues were their tumors that they had developed. So that's really how it started in terms of interest in immune-mediated disease, thinking that I wanted to stop autoimmunity, but then ending up actually trying to induce it and use the immune system as a therapy to treat cancer.
Dr. Venable: Oh, that is really interesting. Talk about a turn of events, right? Like, like to suppress it. Right? And I'm always amazed how cancer has figured out to turn off the immune system. You know, it just, it blows my mind some of these technologies like the checkpoint inhibitors, you know, how they work. It just blows my mind that the body's already doing that. You know, that cancer has already figured out how to go around these normal mechanisms. It's quite insane to me.
Dr. Mason: It's quite remarkable and it's this sort of co-evolution of the tumor growing and sort of this, you know, what we call complex interplay of tumor and the immune system and how the tumor, just as you said, how the tumor can sort of educate the immune system and sort of protect itself. And this is one of the reasons, to be honest, why dogs are becoming so valuable in evaluating immunotherapies because they have developed these cancers spontaneously and they have developed these mechanisms, the tumors have developed these mechanisms to stop the immune system from working appropriately, which of course is what happens in humans as well. And that is very difficult to model in mice or rodent models. So when we're starting to think about using, inverted commas, the dog as a sort of model for human immunotherapies, it makes a huge amount of sense to have a patient, a parallel patient population that has an intact immune system and has spontaneously developed those tumors. It's very important.
Dr. Venable: And that makes sense because when you think about rodents and when you see the studies, it really helps in the beginning to maybe understand some of the mechanisms, but it's such an artificial environment that, yeah, for like what you're talking about, tolerance and things with the tumors, it just doesn't quite play out. So would you say that's a lot of what you're doing with the moonshot initiative as far as, you know, those comparative studies because like dogs that naturally are getting answer?
Dr. Mason: Yes, that's exactly right. That's exactly right. So I think we shouldn't lose sight of the fact that the rodent models are very important, you know, for sort of trying to look at very specific questions, perhaps about mechanism. And some of the rodent models are becoming really quite sophisticated with some of these genetically engineered mouse models and so forth. But really, on the whole, they do sort of rather fall short in recapitulating that really complex environment.
And, you know, with the moonshot initiative, which now was back in 2016, the idea of that moonshot initiative was really to sort of accelerate scientific discovery and to sort of bolster collaboration amongst scientists, translational scientists, and improve sort of data sharing as well so that we could sort of squash, you know, 10 years of research into five years. And of course, at that time, you know, that was sort of three years or so after checkpoints and CAR T-cells were just sort of voted the breakthrough of the year. So immunotherapy was then and still is, of course, extremely hot. And it became very apparent in that initiative that we needed an additional model, if you like, or as again we like to say parallel patient population, that really could help accelerate those types of therapies in the human space. And many of those therapies at that time and continuing now are becoming engineered or being used in combination to overcome those barriers that we've just talked about. And so you have to have a model that has those barriers. Otherwise, you can't say whether your new therapy or combination therapy has overcome them. And that's really how the dog really sort of rose, I think, to the surface in terms of what models could we use to achieve those or some of those moonshot aims, in other words, accelerating scientific discovery and improving translation into the clinics. So yes.
Dr. Venable: And do you get a lot of MDs or human scientists that are interested in using dogs? Or are they still kind of confused by that whole idea?
Dr. Mason: Yes, that's a great question. So it sort of depends. You know, some people are very, very keyed in and they're fully aware of the dog model, particularly individuals that perhaps are working in the fields of osteosarcoma, where the dog is known to be a good model and has been so for many, many years, many decades. So when you sort of look at particular tumours where the dog has been shown to be a parallel patient population, then they're a little bit more keyed in, but we still meet people who will say, you know, ‘Dogs get cancer?’ You know, which is of course strange to us, but I think it's just that they've never really thought of another species. And I think nine times out of ten, I would say, when people are sort of hear about this, they get really excited about it because, you know, it's a new model for them. But I think most of the time they're sort of super excited to think about doing something in the dogs because who doesn't want to do that? You know.
Dr. Venable: They are a fun, patient population, that's for sure.
Dr. Mason: Yeah, absolutely. It's great.
Dr. Venable: How do you see the moonshot initiative evolving, and what role do you think veterinarians will continue to play in that?
Dr. Mason: Yeah. So I think that really what we have through the Cancer Moonshot if I can just back up a bit, was, you know, probably about a year after that, moonshot was sort of started, some RFA request for applications came out of the NIH inviting people to apply for these awards. People who were doing immunotherapies or combination immunotherapy in dogs in clinical trials. So they really wanted those very specific types of individuals that were translational researchers that were using, the dog and using immunotherapies to treat cancers in the dog. And so they actually offered five of those awards. And then in addition to that, they offered an additional award that was basically a cohort donating center. So a sort of central group that would coordinate data coming in from those five awardees, you know, won awards.
They were called and, you know, who'd really sort of be responsible for trying to, again, accelerate those types of therapies by providing sort of networking opportunities, collaborative opportunities, by providing some additional funding for collaborative studies, by providing data management systems, by by providing bio statistical analysis, bioinformatic analysis. And so that's really what our network and the data coordinating center within that network does.
So we sort of put together this acronym of PRECINCT which sort of evolved from the Cagney and Lacey days for people that are my age. And that's the, pre-medical cancer immunotherapy network for canine trials. And that consists of a group of really talented individuals that all are joined by this notion, this concept of comparative oncology and comparative immunotherapy. So we have medical oncologists, radiation oncologists, veterinary oncologists, veterinary rad oncology oncologists and radiation oncologists, pathologists. We have bio statisticians bioinformaticians that are all involved in that group. And all bring very special expertise to that group. And so, you know, we're looking in terms of future where do we see the future. We see that group expanding. We see collaborations, sort of natural and synergistic collaborations occurring already. And we think that that will expand more. We've built working groups and will continue to do so. And those groups are focusing on correlative biomarkers. You know, what should we all be looking at, not just within the U01 trials, but what should we all be looking at? For example, now we're all starting to use the checkpoint inhibitors.
What should we be measuring? What we should we be looking at as a potential collective biomarker of response? And would that help us stratify patients going into these clinical trials so those who have the best chance of responding are those that are selected for these types of therapies, and then developing pipelines to evaluate sort of the data, the various omics data, data that's coming out of these studies as well. So we're really trying to work together to provide tools, reagents, protocols, pipelines so everybody's research can move forward quickly and we can help the dogs and the people more at a faster pace. That's what I hope we're going to achieve in the next five years or so.
Dr. Venable: That sounds exciting, and I always love it when people work as a team, right? Like all the different things you're talking, it's a lot of moving parts, but it does all sound very exciting. Sounds like, you know, like you said, can get a lot of cool information and data out of this. What would you say right now you're the most excited about with all of this?
Dr. Mason: Oh, gosh. Well, I'd have to say something rather selfish, which is what we're working on. No, I think there's a lot, actually, that's coming out. That is very, very exciting. You know, in in our lab, we're working, mostly with the cellular therapies. And we were very fortunate to get funded by one of these, you know, U01 grants to look at a relatively novel cell type called invariant natural killer T-cells that are sort of a cross between the T-cell, cytotoxic T-cell, and NK cells. And we're looking at those as an off-the-shelf therapy for canines and showing hopefully that we can do that. We can engineer these cells with a CAR. So that's a chimeric antigen receptor construct that enables us to redirect the specificity of those cells. But I think the key thing about those cells is that they can be taken from a healthy individual. And without really the editing, they can be then put into an MHC mismatched individual, a sick individual, perhaps with cancer, and they can actually not cause graft versus host disease, and they can mediate their own tolerance. So what we're really trying to do is sort of go one step beyond the highly edited CAR T-cells and actually sort of envisage a world where you have cellular therapies in bank and you can do a sort of a la carte type approach where just like you go and get your red blood cell transfusions, you could perhaps think of a world where you could go and get a CD19-targeted car for B cell lymphomas and leukemias. Or if you've got perhaps glioblastoma, You might want an aisle 13 receptor alpha two CAR. And you can just go and take it out of the freezer and hang it and drip these cells into your patient. And of course, that dramatically reduces the costs associated with autologous therapy. It enables us to treat a lot more patients, right? Because nothing's useful if you can only treat 10 dogs or 10 people. So we have to think about that as well. So, you know, we would be able to spread this out and be able to treat way more patients, be they human or canine. And we'd also be able to hopefully overcome this issue of many patients, dogs and humans, having intrinsic T-cell dysfunction because of their cancer or because of the chemotherapies they've received.
So remember, these therapies are made from initially, right now, they're made from the patient's own T-cells, and that's the drug. So if your own T cells don't work very well, you don't have a very good drug. And so the idea is to use healthy cells from a healthy individual and use those, but there's a number of barriers to that approach. And we're working on that to try and overcome that and those studies are going on in parallel in the human field as well. So long answer to your question of there's other things I'm very excited about too, but that's one of them. And I think it's quite futuristic to think about that. But I think it's coming.
Dr. Venable: I get why you're excited, because that does sound really exciting. Like if you could just, like you said, pull it off the shelf. Because right now, cart tea therapy, we don't use it a whole lot in dogs and I think a lot of it's well one there's not much commercially available but it also seems like it's quite cumbersome and that and that's what you were saying but this what you're hoping you know have a ways to go, but what you're hoping would not require all those cumbersome steps is that right
Dr. Mason: That's exactly right. If we're using an autologous system the patient has to come into a center that has an aphoresis facility. You can get away with a large blood draw, but apheresis, we think is probably better. You know, it can take you 10 days to generate the cellular therapy, to test it and so forth, to make sure it's safe and it sort of works in vitro and then to put it into the patient. And many times these patients really don't have those, that sort of time, if you're going into a dog with relapsed, you know, B cell lymphoma, you don't really want to be waiting two weeks. You know, you'd like to go off the shelf right there and then. And of course, then there's the next generation beyond that, which is now being evaluated in research labs, which is actually making your CAR T-cells in vivo. So, of course, this doesn't overcome the issue of not having great T cells, but actually, you know, taking that construct into the body and actually targeting it to your own T cells, so you make the CAR T-cells in your own body. And all of this really is being directed towards how can we bring this incredibly promising approach, which is really, I'm going to say curing individuals, human individuals with B-cell leukemias and lymphomas. How can we make that more available to everybody and it has to really go off the shelf. And those are two ways that people are looking at it and we're looking at it too in the dogs.
Dr. Venable: Yeah, that is exciting. We'll certainly have to keep an eye out for that. And you know, is this something, because you also have a lab called Vetigenics, which I'd like to learn more. Is this at all involved with that or is that a completely separate group?
Dr. Mason: So it's a separate group. This came out of, again, actually, a CAR T-cell project when I was in Carl June's lab, where I met Professor called Don Siegel. And he is one of the world's expert in something called phage display. And so what this does is he can basically generate these libraries, and they will express antibody fragments on the surface of these viral particles. And you can make these huge libraries that contain billions and billions of antibody fragments. And using some very simple techniques, you can actually isolate out the antibody fragments that stick to your antigen of target of interest. And these antibody fragments we call single chain fragment variables or SCFVs. It's not really that important, but these are the portions that go on the surface of your CAR T-cells, and these are the bits that redirect the specificity. So that's how I sort of bumped into Don and we were sort of saying, “Hey, you know, it would be great to make a canine phage display library and we can do that from leftover splenic material from dogs that are having a splenectomy because they've got a hematoma, not something malignant, but a hematoma or ruptured spleen.” So we did this. So we got some leftover splenic material that was being discarded. And we went down, we extracted the RNA, which of course encodes for all the heavy and light chains of the antibody. And we made this massive 40 billion transformant canine phage display library. And as we were doing that, another RFA came out from the NIH for wanting individuals to generate reagents that could be used in the dog because they were recognizing that, you know, if we're really going to sort of dive into using the dog as a model, we need reagents and we need biosimilars. You know, we can't sort of say, oh, let's use the dog for some checkpoint inhibitor studies if we don't have checkpoint inhibitors for use in the dog.
So it was very fortuitous that this RFA came out and said we want people to make reagents to use in dogs. And so Don and I sort of looked at each other and I were like, “Wait a minute, we've got that.” So we applied for this grant, but the grant was a small business grant, which meant you had to have a small business to get the grant. So that's really how we started Vetigenics. And we started making the checkpoint inhibitors, anti-PD-1, and anti-CTLA4, both of which are now in clinical trials, the PD-1 with urethelial carcinoma and the anti-CTLA4 in oral melanoma in combination with radiation therapy. And we're working very closely there with Mike Nolan at North Carolina State and Jeff Bryan at Missouri, who are fabulous to work with. And it's really a lot of fun and we're learning a lot. And so we're very excited about that. And we have another whole bunch of these things in the work. So we're really excited about the impact that this could make in veterinary medicine, not just cancer, but in other aspects of Canaan health as well.
Dr. Venable: So being a small business, do you think, you know, things go well with the checkpoint inhibitors? That's something that will be commercially available, like through you guys? Or how do you envision that? I realize maybe this is a little too far down the road, but, you know, being the clinical oncologist, that's what I'm thinking.
Dr. Mason: No, Absolutely. So yeah, that's the hope, right? You know, it's a process. So we have to show, of course, initially sort of safety, tolerability, and we have to show efficacy. So that's what we're doing currently. But yes, I mean, you know, when you see these checkpoints and what they can do in human medicine, to be able to actually bring that into a veterinary field safely and in a cost-effective way so that people can afford them is really our sort of goal.
Dr. Venable: That's what we're aiming for. And I think what we're most likely to see is these coming through and then being utilized in combination therapies. We do know that checkpoints don't work in everybody. They work in maybe 10 to 30 percent of people. And I just think that that's a tough sell in the veterinary world to provide a drug that can be quite expensive if you've got a one in 10 chance of responding. So what we're very interested in trying to look at is correlative biomarkers of who does respond. And so, you know, if you've got a correlative biomarker, I mean, not there yet, but if you have a biomarker that says, you know, Fred's going to respond, then I would be more inclined to use the drug for Fred. If George isn't going to respond, I'd be more inclined to start thinking about something else. And I think that that's how we're going to start to see oncology progressing now, is it's sort of going to be identifying perhaps some of the molecular signatures, perhaps some of the targets, perhaps some of the immune environment of the tumour, and then pick your treatment based on that for that patient. So again, sort of futuristically, I'm not sure in the future we're going to look at hermangiocoma, for example, and everybody's going to get docs. I think we're going to look at hemangiosarcoma and say, “Ooh, you have this molecular subtype, so you're going to get this treatment, and you have this molecular type, so you're going to get a different treatment”, you know. And I think that that's probably how it's going to go. It's certainly how it's going in the human field.
Dr. Venable: As I've heard in people with checkpoint inhibitors that, like you said, unfortunately, a low percentage is who responds, but when they respond, it's pretty fabulously, is what I've heard, like cases you wouldn't expect. So I wondered about that in veterinary medicine, too, because like you said, that's kind of a hard cell, especially when it's expensive. So when you're talking about molecular signatures, are you referring to like the gene sequencing? Like we've got a couple groups in veterinary medicine that are doing that. So you think like better utilizing or understanding that potentially might help with some of this down the future?
Dr. Mason: Yes, absolutely. I think so. I mean, they're looking, so there's sort of two things here. When we're looking at checkpoints, people have sort of looked at tumor mutational burden. you know, how genetically mutated is your tumor with ideas being that the more foreign you look to the immune system, the more likely you are to have an endogenous T-cell response that's there, but it can't work very well because of these checkpoint molecules that we've been talking about because of the tumor sort of expressing those and inhibiting those T-cells. So perhaps those are cancers that actually are going to be more likely to respond to checkpoint inhibition. And we know, you know, the tumor mutational burden generally across the board is not really as high in dogs as it is in people. So we have that to sort of contend with. Interferon-gamma signatures within tumors, for example, have been shown to correlate with response to PD-1, PD-L-1 inhibition. So I think we need to do all these sort of things to be able to say you have a tumour that is likely perhaps or more likely to respond to a checkpoint.
Talking about molecular signatures, that's sort of looking perhaps a little bit more at some of the oncogenic drivers of the cancer. So in the example of hemangioma, for example, we know that there now are different molecular subtypes. A number of groups have shown that. And we know that some of them appear to be driven by PIK3CA mutations, and some of them are driven by NRAS mutations. And that seems to be mutually exclusive. So if you've got to PIK3CA a mutation, you don't have NRAS mutation and vice versa. And then you have pairings of P53 mutations throughout. But you know, could we get we're not there yet, but could we get to a situation where, you know, we can look at inhibitors specifically of interest or inhibitors specifically of PIK3CA. You know, could we look at those and see do you get improved outcomes with this. Could this concept of precision medicine, which again is where the human field is going. So targeted sequencing panels will tell us a little bit about tumor mutational burden will tell us a little bit about the types of pathways that are activated. And give us a little bit more information about what we could treat the patient with that will really specifically target that pathway in that cancer in that patient. And I think that's where we're going. And we really want to of course, ultimately bring the the price point down. So that that becomes as common as the histopath.
Dr. Venable: Yeah, that would be great. I do think the cost right with all of this stuff and and some of the targeted therapies, I find that sort of an issue. You know, between one, we're still learning about a lot of these drugs and dogs, but also the cost steps. And just out of curiosity, at the University, do you guys compound or do you use the commercially available or do you guys not really do targeted outside of clinical trials at this point?
Dr. Mason: So at the moment, our targeted therapies are all sort of clinical trial-based. But you are exactly right. The cost, for example, of making monoclonal antibodies, is really, really high. But then if you start to look at drugs like Cytopoint and Librela, you know, the price point is coming down. So it is becoming more feasible to generate cheaper monoclonal antibodies. And of course, we're always thinking about how could we get around this cost. And one of the big issues with monoclonal antibodies is, you know, you have to sort of grow up all this sort of protein in these large, vats and then purify it and so forth. Vial it and so on. So it is expensive. But now sort of we and others are starting to look at, could we actually get the dog to make the antibody, him or herself?
So looking at the taking sort of a leaf out of the COVID vaccine book where we can deliver mRNA, that in the COVID vaccine case, you know, encodes for a portion of the COVID virus, which your body makes, you know, instructed by the mRNA could we do that with monoclonal antibodies? Could we actually give the mRNA that encodes the variable heavy variable light chains, the actual whole antibody, really? Could we actually give that to a dog and could the dog make their own monoclonal antibody. Then we don't have to grow it in cells and purify it because the dog's going to do it all for us. And that again is sort of a futuristic, view. But that is something that a number of people are working on now trying to use sort of non immunogenic lipid nanoparticles to deliver that genetic information that can make the dog make his own antibody. So we can sort of sit back and have a cup of tea while Fred makes his own monoclonal antibody. And that would be a wonderful thing.
Dr. Venable: Well, I love how you guys are thinking about ways around the some of the practical issues. Right? Like you said, that not just we want something that works, but practically, are we even going to able to use it because it's not very helpful if you have a great drug that nobody can use, you know? So that's really exciting. All the different, I never thought about this stuff, but this is really exciting. I like where you guys are trying to go with everything.
Dr. Mason: Yeah, I think it's something we do need to sort of think about, you know, so I think at the last count, there was something like 400 or 500 of veterinary oncologists in the country. You know, you guys are really rare. And so, you know, and you're super busy because you're so rare. So, you know, if it's going to take 90 minutes to infuse an antibody intravenously, that becomes a practical problem, right? I know that the oncology nurses are doing all of that, but still, it ties up some time. And so, you know, if you could give perhaps a short IV injection or an intramuscular injection, then that sort of starts to open things up, you know, and and maybe we do have to start thinking about a different way that we are going to be able to get this out to everybody so that everybody can benefit. I do think we have to think a little bit about that in future, but we're sort of, a little bit of a way off. But we're very cognizant of that and of some of the problems. And we're certainly talking to lots of people, veteran oncologists, internists, and also the people who own the pets as well. To understand this a little bit more and see how we can address that.
Dr. Venable: I think that's great. And you know, something else I get asked about from veterinarians. And I'm just curious too. You know, we mentioned the listeria vaccine that you were working on with osteo. So where I heard, I think it was last year at VCs, kind of the trials that's going on. And mostly, you know, young adults, mostly, you know, they're using that. But what about dogs? You think it's going to circle back around to us?
Dr. Mason: So gosh, yes, I hope so. You know, that was a steep learning curve, you know. You know, I think what we see there is and we're just actually getting ready to publish the paper from the COTC study. I won't spill too many of the beans there. You can wait for that one. But I think what we're learning there is that it helps some dogs. And again, it always goes to this. How could you tell who's going to respond and who's not going to respond. And once you can do that then you can start. If you know that, then you can start to think about, is there a way we could turn a non responder into a responder. You know, is it that you know there's this is if they don't respond if there's very high levels of PD-L-1. Well then perhaps Listeria with a checkpoint could actually be something that we could think about the combination of therapies. So I think you know I'm sort of hopeful it will come back around. We are starting to get some ideas of who does well and who doesn't do well. And this may well be related to how fit your immune system is, you know. And that makes total sense if you are vaccinating a patient and they can't respond to that vaccine because their immune system is shot for whatever reason, then you know, that's not going to be a good patient to receive the listeria until you can understand how you could turn that around. So, I'm certainly hoping that that will come back. That's a nice off-the-shelf product. Right? It's not autologous. And I think we just need to learn a little bit more about who is likely to respond. And probably the next studies if we can get sufficient funds to do that. Next studies are probably going to be combination with checkpoints.
Dr. Venable: And is there any one commercial or even research that people could submit to to find out if the tumor has PD-L-1 or, you know, some of these other changes? We've seen this in tumors. Do you know, is there anybody doing that or is that purely still research at this point?
Dr. Mason: So I think it's mostly research. I stand to be corrected. If somebody out there Antech or IDEXX are like, no, we're doing it. But yes, I think mostly, you know, Iohk is being used. People are obviously looking at, nano string assessment of these tumors as well. So gene expression profiling the tumors and looking to see what what's happening there and what might be in there, what's being expressed. But I think, you know, I see is probably the way that we would go with that on the tumor. And there are antibodies out there that can be used. I'm not sure whether it's being offered commercially yet or not.
Dr. Venable: Okay. I was just curious because I, you know, because you bring up a lot of good points, but I'm like, I don't know if anyone's doing that, but I thought if you knew then that would be great.
Dr. Mason: Yeah. But again, you know, it's complicated. You know, in the human world, they've shown that PD-L-1 expression, for example, on certain cancers, predicts response to anti-PD-1, anti-PD-L-1 inhibitors, but it doesn't in other cancers. And it depends on what you're looking at. Are you looking at PD-L-1 expression on the tumor, or are you looking at PD-L-1 expression on the tumor infiltrating immune cells? And it seems that that actually correlates better with the response to these PD-1, PD-L-1 inhibitors in those particular cancers. So it's not a one-size-fits-all. It's complicated. Unfortunately. So I think, you know, just just sort of saying does the tumor express PD-L-1? It's a definite start. I think it's a definite start, but it doesn't it's possible that it's not going to be the be all and end all. I think it's going to be more complex than that. And we're going to have to have 2 or 3 things to look at, to try and really sort of hone in on those dogs that might respond or not.
Dr. Venable: Yeah, that makes sense. You know, I think we've even seen that with the KIT mutation in mast cell tumors.
Dr. Mason: Yeah, exactly. Yeah. Yeah. It's complicated. You know, that's something that nobody ever likes to hear that that that's the truth of the matter. And we obviously take a lot of what we're looking at from the human field, but we're still to learn whether that actually plays out in the veterinary side of things as well. There's a lot to learn.
And this is why, as you just pointed out, these sort of collaborations are so important and people working together. And that's on all levels, right? It's the researchers, it's the internists, oncologists, whatever you're doing, what you're doing, oncology or some of the auto immune targets that we're looking at. You know, it's the general practitioners referring the cases. It's the owners who need to know about the studies and know about the trials and get involved, you know, informing people about what's going on is probably one of the biggest challenges, because we all live in that world, right, of of experimental therapeutics. But when you go outside of the ivory tower and outside of the specialty practices, you know, a lot of people don't know about these things. So educating people is really important about that. And these trials are available as more and more people doing it. There's are lots of people across the country, super, super smart clinician-scientists that are doing these types of of clinical trials in immunotherapy often times very well funded. So they are essentially sort of free for, for the owners. And to get that information out there, we need to sort of be able to have good solid recruitment and sort of be able to accelerate these studies so that we can learn and move on and keep going.
Dr. Venable: Oh, I totally agree. And where is a good place that you would recommend people looking up? As far as you know, where are all these studies? Is there a good website that you think people should check out?
Dr. Mason: Yeah, so there's the probably the best one is the AVMA website that lists all the clinical trials. And I think, you know, all of the trials, when people setting up trials, they're going there and they're putting their trials on their we have the, you know, one studies on our PRECINCT, precinctnetwork.org, website. And then of course, each university from their clinical trials groups will have their trials listed as well. So, you know, hopefully, some of these trials are listed in 2 or 3 places. And then I think again, we're all pretty good at when we talk to owners sort of saying, you know, we don't have anything, but maybe you should go and talk to, you know, Tim Fan or Cheryl London or, Rob Rebhun and so forth. And they have something. So I think it's nice to be able to do that. And we do do that. And people sometimes are willing to travel.
Dr. Venable: You know, I think that's great. And trying to figure out where to lead people, because there are a lot of people that are interested in trials in it. And I think a lot of pet owners, they like the idea of of helping, you know, it's like, well, you know, my pet, this is a terrible situation. But if I can help the science or help other pets down the road, I find a lot of them really want to be involved.
Dr. Mason: Absolutely. It's absolutely remarkable. I am just blown away each time I see one of these owners who comes in and they coming in with this, you know, very valuable pet, emotionally part of the family clearly, and they're faced with a really poor prognosis. And I would say nine out of ten of them come in and they sort of say, obviously, if this can help him, this is great. But, you know, if it can help another dog, that would be really good. And so, you know, I would be like, help my dog, you know, but they're amazing. They're absolutely amazing. And they've become well, you know, this, you know, they become an integral part of the team. You know, they're at home with the dogs every day watching them, observing them. Are they doing well? Are they doing poorly? They're often filling in their questionnaires. Right. Their quality of life question. They're really they become extremely invested as you and your listeners will know. And it's really it really is a true privilege and pleasure to work with these people. Everybody's sort of working together to to see if we can come up with something that's safe and effective and can help their dog and others. Yeah.
Dr. Venable: Well, I think this has just been such a fantastic conversation. I love all this stuff you have down in the pipeline, and how everyone is working together and really trying to think of better therapies and practical. And I just so many great nuggets to take away from this. And as we're kind of wrapping up, I always like to ask people, who would you recommend as another guest on our show?
Dr. Mason: I would say that if you haven't already had this particular individual, I think he has some incredible work coming through, and that is Duncan Lascelles at North Carolina State University. And so Duncan is actually an anesthesiologist turned pain guru who's been intimately involved in the work with NGF, and anti-NGF. But he has some fascinating data about how, I don't know, I'm not going to butcher his work. But how pain can influence cancer progression. And it's completely out-of-the-box thinking. And he has some very compelling data to suggest that that is the case. And controlling pain could, in actual fact, have positive effects on preventing or slowing down metastatic progression, which is something certainly I had never really thought about before. So if you want something out of the box with some really good, solid science, Duncan is the man.
Dr. Venable: Oh that's great. No, I, I will need to look into his stuff because I hadn't heard that. But I'm like, you know, you know, we want we want animals to be comfortable. But I never would have thought about it actually helping the disease. So that that is fascinating. We'll certainly reach out to him. That's perfect.
Dr. Mason: Great. Yeah. And tell him that I recommended him and he owes me a beer.
Dr. Venable: Will do. Well, I'll do for sure. Well, thank you, Dr. Mason, so much. That certainly has been my pleasure. And thank you again for being on our show.
Dr. Mason: Thank you so much. It's been an absolute pleasure. Thank you.
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.