34. Trailblazing Approaches to Sarcoma Treatment

Lab Rat Chat - Episode 34 with Dr. Ben Wylie

Get ready to embark on a fascinating scientific journey with our esteemed guest, Dr. Ben Wylie.  We know you're curious about his career journey, his cutting-edge work in sarcoma research, and his innovative approach towards cancer treatment. So, we promise you an enlightening conversation that is sure to feed your curiosity and inspire your scientific spirit.

In the first part of our conversation, Dr. Wylie takes us through his journey, from his childhood fascination with the natural world to his current role in cancer research at the Telethon Kids Institute. He opens up about his career transitions, his love for academic research, and the critical work his team is doing in pediatric sarcoma to utilize a biodegradable material to deliver immunotherapy during surgery. This approach, which targets invisible micrometastatic disease left behind during surgery, could potentially transform the landscape of post-surgical cancer treatment.

The conversation takes an exciting turn towards veterinary research and the canine clinical trials to test the efficacy of their immunotherapy gel in dogs diagnosed with sarcoma.  We discuss what hopes to be very promising results from this trial and how it can hopefully be translated into the human world.  Stay tuned, and prepare for a thought-provoking ride into the world of scientific innovation.

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Resources & Links:

• A surgically optimized intraoperative poly(I:C)-releasing hydrogel prevents cancer recurrence - PubMed (nih.gov)
• Sarcoma Translational Research | Telethon Kids Institute
• World-first clinical trial in Perth could lead to breakthrough treatment for children with sarcoma - ABC News

Transcript

Speaker 1: 0:05

This podcast is supported by Americans for Medical Progress and was founded and created through the Michael D Hare Fellowship, awarded annually to support projects that inform and educate the public about the critical role of animal research in furthering medical progress. The Fellowship honors the late Dr Michael Hare, a renowned board-certified laboratory animal veterinarian who dedicated his career to scientific and medical advancements and who was deeply committed to animal welfare and advocacy. We've got Dr Wiley with us today. He's going to talk to us about some sarcoma research some really cool stuff they're doing there. As part of our promotion of July is in the US, new A's National Sarcoma Awareness Month. He's going to give us some really good information about what sarcoma is, some of the research they're doing there. Now let him tell you all about that.

Speaker 1: 1:01

But before we get started, I do just want to tell everybody out there to please go on social media rate review our show, make comments on our posts, follow us on Instagram. If you're listening to this, on Spotify, apple iTunes the great thing is this is not live. You have the opportunity to press pause. Rate review the podcast. It really helps our exposure. More people can find us, more people can hear us, more people can find out about what Libra chat's all about. So thank you for everyone for doing that. We've noticed more and more followers lately, and I think it's all because of our dedicated listeners out there. So thank you for that. And with that, let's go ahead and get into today's episode. So, dr Wiley, if you will just tell us a little bit about your background, what made you so interested in research and science, and just give us a little description of the journey to get where you're at in your career today, Thanks, jeff, and of course, thanks for having me on the podcast.

Speaker 2: 1:52

It's fantastic. I think the work you guys are doing you know, telling everyone about the awesome research that's going on and all the animal work that we're doing is really important. So I think most people's journey into research and certainly my journey starts with curiosity. It's probably the key aspect of you know what drives people's desire for research, and it's really that wanting to understand why and how things work. And for me that really started off early on in my life in thinking and looking at the natural world. So I was really interested in animals documentaries and I actually wanted to be a veterinarian at a very early sort of young age. Didn't quite get the grades to do that straight out of school, so I chose actually to go to university and study biomedical science and from there that's really where my research interest sort of was first piqued and the research journey began. I think the real like revelation for me came in finding a topic that I was really interested in and that was, you know, a third year university. You know that I taught in immunology and learning all about the immune system, how everything worked, all the things that were going on inside my body. That was really fascinating. And at the same time I did a research project over the summer break at uni and I worked in a lab that was focused on the genetics of wheat fungus, which I thought was really pretty boring, but I knew I liked working in the lab. That showed me I liked working in the lab. So from there I had this idea that's where I wanted to end up doing research. It took looking around for you know, a few different jobs to find a place where I could really apply that for immunology in an area that I felt could have a real positive impact, and that ended up being in cancer research. And so, you know, I had a couple of research assistant jobs where I learned a lot of skills and that really led me on to, you know, my PhD, which was at the telecom kids institute, working in the cancer center, and there I was looking at specific immune cells called dendritic cells and they have a role in your body which is to detect cancer and other things like viruses and bacteria and to activate your immune system to destroy those pathogens. And really when I was starting my PhD, we were just sort of learning that your immune system can be activated to destroy those cancer cells, and the first research was coming out of labs in America showing that there was real potential in using this as a therapy for cancer patients.

Speaker 2: 4:00

So my career path didn't necessarily always take that straight line, like you might think. There have been times where I wasn't certain what my research future was going to hold. After my PhD I took a bit of a left turn. I took a job at a local drug discovery company and I worked there for a couple of years developing a range of different therapies across different areas, and that gave me a really good look at, you know, the commercial side of research, which is really focused on pushing a drug candidate to the clinic, and that was kind of refreshing because it wasn't something I'd done during my PhD.

Speaker 2: 4:28

My PhD research had been very sort of fundamental, but some people call basic research about you know how the cells of your immune system function and interact with cancer, so that was really interesting. However, I still felt that pull from you know academic research, like I still had something left to do, something unfinished there, and so when the chance came to sort of move back to Telethon kids with a new group that was starting up there, I jumped right in and I haven't looked back. And that group is the sarcoma group. They're looking at developing new, safer and more effective ways to treat pediatric sarcoma and help kids who have this terrible cancer.

Speaker 1: 4:59

Yeah, that's awesome.

Speaker 1: 5:00

It seems like it's a cancer that does affect, unfortunately, a lot of children.

Speaker 1: 5:04

I can definitely relate to a little bit of your journey about not having the greats to get into vet school. I didn't have a right out of undergrad and out of getting my master's degree and ended up as everyone that listens to this show knows, because I say it over and over is I had a 10 year gap between graduate, my undergrad, until applying to vet school and really I didn't have these huge intentions of going to vet school right away and it was something that my career within the field of biomedical research led me to wanting to go to vet school. But had I tried to apply to vet school right out of undergrad? There's no way, and so I was able to kind of build up my resume by showing all this experience with animals and in that way. So I'm thankful for my journey and no one really has that straight path to get to where they are, and I think that's what makes everyone's story so interesting and it's always cool to hear everyone's story and background, so appreciate that.

Speaker 2: 5:51

It's funny I'll touch on it a little bit later but I actually almost converted over to vet school during my undergrad degree and one of the reasons that I thought I'm not really sure about vet school is because I wasn't sure how I would handle having to do surgery on animals. And I guess as I'll touch on a bit later you know, in my current project that's actually one of the things I've gone back to and a skill that I've learned. So it's funny how these things come around.

Speaker 1: 6:10

Yeah, absolutely so, all right. Well, since July, let's say, I know it was actually August 4th, so for everyone listening, we didn't get this out in July, but July that was our intention. Scheduling can be difficult when we're halfway across the world. July is our coma health awareness month. So let's first you've already talked about it a little bit what exactly is sarcoma, you know? Just give us some background on that, as much information as you can about you know how many people might be living with it. Is it aggressive, non aggressive, that sort of thing.

Speaker 2: 6:39

So sarcomas are really a group of cancers. We kind of linked them all in under this one name of sarcoma. But they're generally solid cancers that form in the connective tissues of your body. So these can be things like in the muscle, in the fat around nerves and just generally in the connective tissue that holds your body together. Sarcomas are actually reasonably rare in adults. They're actually much more common in kids. They're the third most common cancer, behind blood cancer and cancer in kids, although overall, thankfully, childhood cancers are actually very rare in comparison to cancer in adults. So I think in the US the total is about 15,000 people a year diagnosed with sarcoma and about a thousand of those will be kids. At the Telethon Kids Institute, where I work, we're really focused. We're a kids research institute, we're focused on pediatric oncology and pediatric cancers and for kids sarcoma is a very serious disease. One in three kids still die from sarcoma, despite our best efforts and the best current therapies that we have.

Speaker 2: 7:33

And indeed sarcomas can be quite locally aggressive and because they're a solo cancer, the main sort of first intervention that an oncologist will normally prescribe is a surgery to remove a lump. So anecdotally, we hear these stories of kids. Actually, you know they'll have a bit of a lump somewhere on their body. It's actually quite interesting. Often they'll have like a sporting mishap or an injury, or they'll fall over and bump their leg and they'll say, oh, that really hurts. And they'll tell their parents that they've got this bump. That hurts and it just doesn't seem to get better over time, and then so that results in a trip to the doctor and, you know, a biopsy or something of this lump, and then often it turns out to be a sarcoma. We call this a solo cancer. It's a lump. It can be removed surgically and that's generally the first treatment that is prescribed. The oncologist or the surgeon will go in. They'll do a surgery to try and remove all of the sarcoma, if they can.

Speaker 2: 8:21

Often because sarcoma is involved in connective tissue, so around the, around the organs involved with nerves, it's often not possible to remove all of that cancer in one go, and so this is one of the main problems with sarcoma. They're quite locally invasive and aggressive, and because surgeries aren't always effective, it means that the patients have to have follow up, chemo and radiotherapy. It's also quite interesting. We do interact with both adult surgeons and then the pediatric surgeons at the hospital that we're located in in Perth and the kind of surgeries that they'll do are also quite different.

Speaker 2: 8:53

So the kind of surgery that you might apply, the surgical approach that you might apply in an adult is very different than in a pediatric patient as well, where they there's a real preference not to do, you know, major surgery, not to limb removal surgery and things like that, because obviously that's going to massively affect a pediatric patient or a child's ongoing wellbeing and state of life throughout the rest of their life, even if they are cured of their sarcoma. It's really on us in the research side to start coming up with better therapies that can help these kids with sarcoma. That's what our lab is all about. We say it telephone kids and in the cancer center we're all about developing safer and kinder therapies for kids.

Speaker 1: 9:28

So in like in dogs for example, osteosarcoma is a really big one. Is that pretty common in children also? Is it more soft tissue?

Speaker 2: 9:36

The three big ones in kids are osteosarcomas, and then there are a couple of soft tissue sarcomas which we're sort of interested in particularly, and then another group which are called rabdomyosarcomas, and these are the ones that form in the muscles Interesting in kids. They all affect slightly different age groups as well, so some will affect very young kids, some will really affect the kids as they're becoming adolescents and young adults. So turning into teenagers and young adults, there's a crossover there in the clinicians and how they're treated when they're sort of transitioning through that phase from being an older kid to a young adult, to a full adult, and that can affect the kind of cancer treatment that they receive.

Speaker 1: 10:10

Yeah, absolutely, and I guess the success rate on their treatment is going to depend on many variables, such as how early they catch it, how invasive it already is, whether or not it's already spread and that sort of thing.

Speaker 2: 10:21

Yeah, of course.

Speaker 1: 10:23

So yeah, since you already talked about some of those treatment options out there, just tell us a little bit specifically about your team's research and that novel type of I believe you guys are doing some immunotherapy delivery and a unique system. So how'd you guys come up with that idea and then talk to us a little bit about some of those results so far?

Speaker 2: 10:42

Yeah, sure, I mean I'll touch on the current kind of state of play, I guess, because it's important to know that there's a lot of research that's gone on over the last 30 to 50 years for cancer patients around chemotherapy and radiotherapy. The number of people surviving these cancers is, you know, we've done really the best that we can, but for sarcoma in particular and in pediatric patients, the state of play hasn't really changed for maybe 10 or 15 years. They haven't been those steady improvements anymore with those kind of traditional therapies and that's why we're really focused on immunotherapy. The other reason that I think the whole of the Telephone Kids Cancer Center, where I work, is really focused on immunotherapy is we know that chemotherapy and radiotherapy they do require high doses of treatment. There can be toxicities associated with these treatments and in kids particularly, these can be long-term developmental side effects that can really go on and affect the kids after for a long period of time, even after they're cured of their cancer. So immunotherapy for us represents a way to, you know, potentially increase the rates of people that were curing of cancer, while also reducing those side effects that we see from chemotherapy and radiotherapy. And that's really, I guess, where this whole project was born from Anecdotally my PI, who's the head of the lab that I work in.

Speaker 2: 11:53

He began his life as an oncologist before moving completely to the research field, so he was so in love with research he sort of saw the need for research being so strong that he completely jumped over to the research world and now is 100% focused on cancer research. He was actually working with orthopedic surgeons at a certain time while working with sarcoma patients in his oncology clinic, and that interaction sort of led him to this idea. In orthopedics, often when they're doing something like a hip replacement, they'll place something in that wound site which is either coated or embedded with antibiotics to try and prevent infection after surgery, and so that sort of sparked our idea is to well, if we can use a material to deliver antibiotics during surgery, why not a material that we can actually deliver immunotherapy during surgery as well? And this really sort of became up with this concept of surgery being this window of opportunity. Right where the surgeon has gone in, they removed all of the cancer that they possibly can. Sometimes they know they've left some behind because it's involved with a major organ or a blindness or that can't be removed. Sometimes they know there's going to be what they call micrometastatic disease left behind, which is not visible to the eye but they can have pretty sure it's there. And so in this setting where what we call this an incomplete perception of the cancer, we know there's going to be cancer left behind, but it's really about finding the optimal window to apply these therapies where we've got the best chance of them being effective, because we know if this cancer comes back, it comes back more aggressive and harder to treat.

Speaker 2: 13:19

And so this idea it was coming from orthopedics about putting something in the wound to prevent infection we kind of jumped on board with this and ported that over to the cancer setting with this idea of delivering immunotherapy actually intraoperatively or during that surgical procedure, and that really started off for us. What's been this massive immunoengineering project where we had to come up with a treatment that we knew was going to be safe during wound healing, because we can't be doing anything? That's actually, if I step back a step after a surgery, when the wound is healing it's a very immune, active process, right, there's cells coming into that wound to start that healing process. We don't want to give an immunotherapy that's going to affect that negatively and cause wound healing to be impaired. So it's been a real journey in finding the right therapy to combine with the right material to place in a wound.

Speaker 2: 14:06

That's also going to be biodegradable, so it will break down slowly over time and the body will reabsorb it so the patient doesn't have to come in and have it removed later as it's breaking down. It's also releasing that therapy, that immunotherapy, slowly into that local area where we suspect there might be cancer cells left behind and the goal really there is to use that therapy to activate the immune system so it can detect those little bits of cancer that are left behind. You get a flood of immune cells coming in which will then destroy the cancer cells and the surgeon and the patient can be more surgeon that the surgery has actually been effective at removing all of the cancer cells. So not only we think this is going to be an optimal time to apply this therapy, but we're really hoping that it means that also, when we have these kids that are coming in with cancer, that they're not going to have to have this follow up chemotherapy and radiotherapy treatments, which can be really hard on them.

Speaker 1: 14:53

Yeah, absolutely, did you all someone in developing this product? I mean, I know you did some research in dogs with the G. You guys use other animal models and like the developmental phase where you're trying to figure out the best type of polymer or best type of way to get this in and then find a product that's dissolvable. I didn't interfere with wound healing and everything that you went on to describe that you guys needed to accomplish.

Speaker 2: 15:15

Yeah, definitely. So I think it's really. We had quite a staged approach where we started off in the lab in tissue culture, cell culture, testing drugs on cancer cells to find out which drugs we thought were going to be the most effective at attacking these sarcoma cells. So we did quite a lot of screening of drugs in tissue culture dishes and 96 wall plates, which allows us to screen through things really quickly, identify the best candidates, best drugs that we think are effective, and then we take those and we say you know which of these are applicable for loading into biomaterial. So we actually came up with a gel. It's a bit like a hair gel in consistency, that's moldable, still keeps its shape a bit and is really usable by the surgeon. It's optimized for the surgeon to be able to be placed in the wound and so then we took those kind of top candidate drugs, we tested them in our animal models of cancer.

Speaker 2: 16:00

These are mouse models of cancer and the reason that we have to do this in an animal model is that when we want to model an interaction between the immune system and the cancer cell, we just can't really do that effectively in a dish in the lab. So we can't recapitulate that intense complexity that we see in the immune system and all the different cell types which are actually critical. They're all critical in driving this immune response which destroys the cancer cells. We then move from that phase where we're treating, looking at lots of drugs in the lab, to picking our top candidates to then test in our, in our what we call pre-clinical models, which are mouse models. We're looking at the effect of the animals immune system to actually fight cancer cells and you'd be surprised how similar a mammalian immune system is in general. So, whether it's a dog, whether it's a mouse, whether it's a human, there's quite a lot of translatability across each of those species in terms of how the immune system works.

Speaker 1: 16:52

Yeah, especially with mice. I think so many people don't realize how closely immune system wise anyways mice and humans really are and why they're used. That's what we've talked a lot about on the show, about how they use specifically, and a lot of immunological research out there, and I think it's fascinating and I think it's still hard to play. Our listeners find it fascinating when you think about the vast differences between mice and us, obviously, but when it comes to the immune system, there's so many similarities and just the way we can engineer them. I think it's pretty cool.

Speaker 2: 17:18

Yeah, it's actually quite interesting to go back to my PhD for a second. I came out of my PhD research actually knowing a lot about murine or mouse dendritic cells, because that's what I studied a lot and there was kind of a for a long time there was a big gap between how much we knew. We knew so much more about the mouse immune system than we did even about the human immune system, and so it actually took the human scientists and the clinicians a lot of time to catch up to where we were in terms of how much we understood about the immune system, because we could study it so well in these animal models. So what we really arrived at then was after our preclinical animal studies was that we had chosen our best candidate drug and we were able to optimize the gel that we were using to deliver it during surgery, and of course, we had to develop a surgical model for this. So we have a small animal surgical model where we remove a certain percentage of the tumor that the mouse has and then we're actually able to place the gel in that setting close up the wound, recover the animal and then measure the effectiveness of the gel and the drug that we're delivering over an extended period of time and see how that actually prevents recurrence of the cancer. And we're able to show in a number of different cancer types that this drug could be really effective. Not only on its own it could decrease cancer recurrence on its own but it also worked really well with additional immunotherapies. Some of your listeners might have heard of things like immune checkpoint blockade, which is a systemic immunotherapy which is used in humans in clinical trials and now in melanoma and lung cancer and can be really effective. And we found that by giving this local therapy in the gel we were actually able to like, sensitize some of these cancers to respond better to these other immunotherapies, which was really promising, absolutely.

Speaker 2: 18:55

And then the next step was to say how do we make that leap from doing a surgical model in a small animal, in a mouse, which is we're talking about 20 grams, scaling that up to a human, that's 20, 30, 40 kilos in a pediatric patient?

Speaker 2: 19:11

There had to be an intermediate step and for us the perfect intermediate was by doing this canine clinical trial. So we actually went up to a vet clinic up the road from the hospital and we said to them do you see canine patients? Do you get dogs that come into the vet clinic and they have cancer and they said, yeah, we see these ones, we see these, we see sarcoma all the time. And we said, oh, that's fantastic, we're really interested in developing new therapies for cancer. Why don't we develop a clinical trial in collaboration with the vet clinic? Not only can we test our surgically developed gel that we have in the therapy in the animal model that's more replicative of the surgical procedure that you can do in a human but we might actually also be able to help some beautiful pet dogs at the same time, and if we can cure some dogs of their sarcoma as well, that's a win-win.

Speaker 1: 19:58

Yeah, especially, we see it quite frequently. We see osteosarcoma at least a few times a year and I mean typically we treatment if we can catch early enough is to amputate the limbs and we can wrap and see there in one of the extremities and then if we can amputate, great, but even then a lot of times their median survival time is still 12 months or so and if we had a better way to treat it that'd be awesome.

Speaker 2: 20:19

Yeah, exactly, and I think it's a similar situation. Obviously, not all owners of their pets are willing to sort of make that sacrifice, and limb amputation is a pretty radical surgery and I think that dogs actually manage quite well on three legs when they need to.

Speaker 1: 20:34

I mean that's really an option for humans and of course, that'd be a very radical sort of aggressive way to treat it For dogs. Yeah, most of them, I mean they do great with three legs. They act like you wouldn't even know they're operating on three. Sometimes, when you first walk in, it takes that second glance to look down and go there's only three legs instead of four, just because they can ambulate and get around so well.

Speaker 2: 20:54

Yeah, for sure. We think that the gel, though, will be that additional therapy on top of surgery where, like I said, if we can hit the cancer at that point where we hope it's at its weakest the surgeons removed as much of the cancer as they can. We just need to activate the immune system to do its job. We know that these immune cells are already coming into that wound area. If we can just give them the right signals, activate them against any cancer that's left behind and clean that up, that's really going to help prevent recurrence of disease and disease relapse, which can ultimately be what ends up causing the death of some of these patients.

Speaker 1: 21:26

Absolutely so. With the clinical trial, you all have numbers on how many dogs you guys treated or solved with sarcoma and implied your polymer immunotherapy treatment too. What's the data look like from that?

Speaker 2: 21:38

Yeah, so we've just finished recruiting all our patients. We have one of our dogs has to come back in and give his like three month follow up blood sample. So we asked the patients the dogs to come in and give blood before we did the surgery and then at two weeks post-surgery, when they would normally come in and have their post-doc checkup, we asked the vets to take another sample of blood and also to look at the wound and make sure it was healing all right and that there wasn't any complications with that wound healing. Like I mentioned, we really needed to make sure we're avoiding that. We definitely chose drugs that we knew weren't going to affect wound healing in our mouse models. In fact, sometimes they even made the wound healing better. So we're pretty confident that it was all going to be. You know, we had a good data set pre-clinical models. We're pretty sure it's going to be fine. We just needed to make sure in that larger surgical setting that we're seeing, you know, a 30 kilo Labrador is kind of a good model for a child in some regards in terms of the dose of drug and the size of the surgery that's going on and, yeah, we've had really positive results.

Speaker 2: 22:30

So this was really a trial for safety and usability of the gel immunotherapy combo. So the first thing the vets told us was that the gel was perfect for applying during the surgeries that they were doing, adhered nicely to the wound area, it didn't leak out, they could close up the surgery and then when the patients came back in, there was no signs of complications with the wounds and the gel had degraded naturally over that period and released all of its drugs. So that was really good. The other one was that of course we don't say the vets, you know, we don't want them to leave any cancer behind. We always want them to remove all of the cancer if they can.

Speaker 2: 23:00

In every surgery we just put the gel in there as a you know, a bit of an additive as well. So we need a way to measure how effective the gel is in activating the immune system, and that's why we have these blood samples, which is what we're following up now, and we're using a technique called flow cytometry which in the lab allows us to label all the different kinds of immune cells that are in the patient's blood sample, so white blood cells, things like dendritic cells, macrophages and neutrophils, which are all important in the anti-cancer response and by looking at the blood samples before we do the surgery and give the immunotherapy and then afterwards we can really look at whether there's been a good activation of the immune system that we think is going to be effective at finding the cancer. So it's really exciting. We're just sort of looking at that data now. I can't really say too much about it, but we're really hoping it's going to be really promising and going to show us that we're having a good effect.

Speaker 1: 23:44

Well, I can't wait to see some of those results and then, hopefully, something we can have access to at some point down the road.

Speaker 2: 23:50

Exactly. There's been some really good examples of this translation of drugs through veterinary practice and into human clinical trials as well, and that step has been really important, I think, in speeding up some of these therapies, because it does take quite a long time it can take seven to 10 years to get a drug from the bench into, obviously, bench to bedside where we're actually treating patients in a clinical trial and so by getting that really important early data in something like a veterinary setting, it allows us to really speed up that process. It allows us to de-risk some of the process when we're looking ahead and saying is this going to be a therapy that's going to be effective and work in a human patient? So it really is important for us in the translation of these therapies from an idea that we have to the lab to the bedside.

Speaker 1: 24:35

Yeah, absolutely. You kind of already touched upon this, but in your opinion, is there any way to conduct the research that you all did if you didn't have the availability of using animals in research? So if you just had to realize solely on computer models and cell culture and stuff which you had talked about already, and not have actual live animals, do you think you could still develop the product or in the same timeframe that you guys were able to do it?

Speaker 2: 25:01

It would be very difficult. I mean, scientists are very smart people. I'm sure that we would come up with some way to do that. I can't think of it off the top of my head just because I touched on this all the way through. The human body is so complex. Your immune system is so complex. There are so many different cell types within your immune system which are involved in keeping you safe and healthy and free from bugs and cancer cells. It's really hard to model that in a dish.

Speaker 2: 25:27

People are trying they're working on 3D printed organs, so that's a really cool kind of application that's come out of.

Speaker 2: 25:33

3d printing is now we can 3D print cells and matrices that can kind of replace that structure of an organ and then the cells can grow within that which can give you the right 3D sort of orientation and interaction. But particularly when we look talking about immunotherapy and looking at the response of the active complete immune system against a cancer cell, then it is really difficult to model that Without being able to go through that process in our preclinical animal models. It would be a bit more of a shot in the dark when to make that step to humans and I think a lot more things would fail because we wouldn't have that, all that data generated to suggest that this is a pretty sure bet that it's going to be improved the outcomes of the patients when you treat them. So the bar is set really high when you want to take a therapy into a clinical trial and start treating human patients, and so I think, without being able to work in some of these animal models, it would be a lot harder.

Speaker 1: 26:24

Yeah, really I think a lot of the applicability comes into play. It's not always, I mean, of course efficacy is important and critical, but really you got to have confidence that what you're putting in is going to be at least safe and not cause more harm than you're trying to help. Exactly, I think that's where the animals really come in to help with this research.

Speaker 2: 26:43

We couldn't do the kind of research without the animals, and the benefit that they provide is really huge.

Speaker 1: 26:50

Yeah, it's going to be tough to get people to sign up for clinical trials and doctors to back them if all we have so far is some cell culture data. This wouldn't have that confidence. But, like you said, of course, maybe at some point down the road scientists will develop some sort of new approach that gives us that information without having to use animals. But, like you said, I don't know what that is and maybe at some point down the road we'll find out. But for now we don't have that kind of technology.

Speaker 2: 27:14

Yeah, and I think, like I said, scientists are a pretty smart bunch and we're pretty inquisitive and we're always looking for those new potential things, because that can be another way that we can speed up the research as well, or it can be really nice complementary technique that we can use alongside having to use animals.

Speaker 1: 27:29

Yeah, Absolutely so. We always like and you've talked about this a lot already do we always like to kind of summarize and tell our listeners about how your research can be applied to the human world. And I think if people have been paying attention we can already see how it's going to be applied to the human world. So if you would just kind of summarize a little bit about how your research has helped advance our understanding of like sarcoma treatment options and then how or when do you think we might see some of the results of your research being used to help out humans, particularly these children that are suffering from sarcoma?

Speaker 2: 28:04

Yeah, exactly, thank you. There isn't a lot of information, I guess, out there about delivering therapies during surgery. We know that this is a bit of an underappreciated area and it's a very important area in terms of their immune response. Our goal really in the sarcoma group the telethon kids is to come up with safer, more effective and kinder treatments for these poor kids with sarcoma. We think that that surgical moment when they're having the cancer removed is that window of opportunity for us to apply the most effective therapies that we can at the moment when they are needed. We've really learned a lot, I think, about the practical elements of this. It's been as much an immunological project as an engineering project. We've collaborated with a lot of chemists and bioengineers around. Actually, what kind of gel? How do we get the gels or at least the drug over the period that we need? All the physical properties. We've really learned a lot about drug delivery in the context of surgery and active immune area, I think. Looking forward, we really hope that if we can really nail this on the head and get it working, it's going to provide an entirely new way for surgeons and oncologists to start the living therapy in cancer patients. It can be applicable beyond just sarcoma or beyond just pediatric therapy, to a whole range of solid cancers in adults as well. We've already hoping to potentially see some effect in our canine patients, which would be really awesome. I think our job now is to take all of this amazing data that we've been able to gather because we're working at animals, because we've been able to do the preclinical mouse models, because we've been able to go and test in our canine veterinary patients. It's really our job now to take all that data that we've been able to generate and push ahead towards a phase one clinical trial in human patients With sarcoma. That might be in adult patients first. It might be in pediatric patients.

Speaker 2: 29:52

We're certainly now looking forward. We're looking ahead. We're talking to our collaborators who are oncologists and surgeons at the hospitals that we're co-located with. We're saying to them what's the best patient cohort that's going to benefit from this? Where would you like us to start delivering this? We're also raising money. This isn't a trivial process. It can be. We're looking at even for a small human trial a year in the tens of millions of dollars we need to get that money from somewhere as well. That's a constant struggle in research. We're really out there we're hitting the pavement, we're talking to a lot of people, we're collaborating with a lot of people and we hope to see we'd love to see this kind of therapy which we're pioneering out there in the hands of surgeons and oncologists helping patients with the next three to five years.

Speaker 1: 30:34

Awesome. Well, if we have any extremely philanthropic listeners, help them out. One thing we like to ask all of our listeners is just basically, and I don't know what the culture is like. We did talk to somebody from New Zealand and I know I can't make comparisons between New Zealand and Australia I was already corrected once on that but we did interview somebody from New Zealand. They told us a little bit about the culture of animal research down there and public perception. When you go about talking to people at a gathering, on an airplane, at a party somewhere, about what you do for a living, do you bring up the animal component of your research? If so, how is that perceived and how do you explain to them what you do?

Speaker 2: 31:10

It is a tricky one. You do have to be careful. I guess sound people out a little bit. I focus on two things, and we've touched on them here a little bit as well. Is that really the need that we have to understand the complex biology and actions mechanisms of the immune system that we just can't do in any other way at the moment? I touch on the end point, the goal that we're trying to achieve, which is to develop new therapies to help kids with cancer. To do that translation, we do need often to work in animal models. I also like to tell them a bit about the process that we go through, because I know it's probably the same in New Zealand and in the US as well.

Speaker 2: 31:46

We have quite a lot of process around the ethics approvals that we need to acquire. There are ethics committees with a group of veterinarians, scientists and lay people on those committees that have to approve our applications. We work very closely with our animal welfare officers, who are veterinarians, and we actually designed our surgical modeling in collaboration with our animal welfare officer at the institute that we work at. We do take the best care that we can with these animals. We understand that it's really not optimal, but they have to have cancer and we have to try and treat them and cure them. That doesn't happen all the time, but we do take the best care of these animals that we possibly can.

Speaker 2: 32:22

I like to really stress that I'm an animal lover. I grew up loving animals. I love doing things like I used to go and sit in my backyard and look at all the different bird species that came into our backyard. We were lucky that we had a very lush, green backyard and I would tick off all the different bird species that came in. I've always been an animal lover and I think part of that makes working with animals difficult, sometimes part of it really interesting and it's part of the reason I enjoy the animal work. I just try and help them understand and embrace the animal work that we do.

Speaker 1: 32:54

Yeah, that's a great way to do it. Sometimes it's quite the conversation to have and you have to dedicate some time to get some people to understand and you're not going to convince everybody. Just tell them how it is and let them form their own opinions from there. So I appreciate you sharing that with us. Before we wrap up, is there any final statements or anything that we haven't covered that you think our audience should know regarding your research, animal research in general, sarcoma or any other topic?

Speaker 2: 33:20

We've covered off on all the key points. I'd just like to say thanks, obviously to you, Jeff, for hosting this podcast. I think what you're doing is really important spreading that sort of open and honest conversation about animals in research and it's something that is really important as a research community and communicating our research to the broader public as well. Thanks for leading the way there and it's been a pleasure to talk to you and all of your listeners.

Speaker 1: 33:42

Yeah, it's been great and I forgot to mention in the beginning. Obviously Danielle's usually joining us, so everyone out there wondering where Danielle is. She's just stuck in some monsoon rain in Virginia and has some work things going on, so she couldn't join us today, but she'll be back. It just couldn't make it happen today and I didn't want to try to reschedule today's episode just because of the time difference and everything going on and it would have been last minute. So thank you for being accommodating and staying up. I guess it's not too late over there.

Speaker 2: 34:10

No, it's not too bad.

Speaker 1: 34:11

Thanks for accommodating our time difference and making it happen and sharing with our listeners everything about your research and telling us about Sarcoma, and it would be great to hear. Make sure you follow up with us. When you guys do get some data from your clinical trials and we're able to share some of that data with our listeners, or any publications you guys put out, send them over to us. We'll share them. We'll go ahead and share. If you have links to your research webpage or your institute, definitely send that to us. We'll share it with everyone that's listening to this episode and everyone that's listening to you. You know where to find those links on our social media pages or they'll also be embedded within the show notes of today's episode. All right, so thank you so much, ben, for joining us today. It's been a pleasure talking with you.

Speaker 2: 34:53

It's been a pleasure, jeff, really lovely to talk to you as well.

Speaker 1: 34:57

Absolutely Everyone. Please take a minute to rate. Review our show again. Email us LibratChat at gmailcom. If you have questions, topics, you want us to cover anything of the sorts, we appreciate it and we will catch everyone next time. See everyone, bye-bye.