Dr. Nicola Mason Discusses New Clinical Trial for Dogs with Osteosarcoma Lung Mets, on Tripawd Talk Radio #130

This week, we are so honored to chat with Dr. Nicola Mason, about an exciting clinical trial for dogs with osteosarcoma lung metastasis. Tune in below for Tripawd Talk Radio #130!

Today, you will get all of the details about this important next step to discover effective immunotherapy treatment for dogs with osteosarcoma that’s metastasized to the lungs. Tune in to the podcast, listen on YouTube, or read the entire transcript below.

Dr. Nicola Mason Discusses CAR-iNKT Cell Therapy Clinical Trial for Dogs with Osteosarcoma Lung Mets

If your Tripawd has lung mets, we are so sorry. But if you are in the Pennsylvania area (or able to travel there for treatment), Dr. Mason explains how your Tripawd can be part of this exciting new clinical trial.

Listen to Tripawd Talk #130

This episode follows up on our recent article about her clinical trial, Cell Therapy for Metastatic Osteosarcoma.

We also talk about:

The importance of immune system “fitness”

What pet cancer scientists have learned from past clinical trials

The ultimate goal of “off-the-shelf” cellular therapy for all cancers

And how courageous pet parents who enroll their dogs in these studies are helping to advance care for both dogs and children with osteosarcoma.

Whether you’re facing a recent diagnosis or simply want to stay informed about the future of canine cancer care, tune in! This episode offers hope, insight, and valuable next steps.

Tune in on Tripawd’s YouTube Channel

Learn How Clinical Trials for Osteosarcoma are Helping Humans and Pets

By utilizing groundbreaking CAR T-cell therapy to fight metastatic osteosarcoma in dogs, the findings from this trial may offer new hope for Tripawds and their families.

You’ll love learning about Dr. Mason’s work at the University of Pennsylvania School of Veterinary Medicine (“PennVet”). She’s known globally for osteosarcoma immunotherapy treatment breakthroughs in dogs like Dexter, one of the earliest dogs to receive an immunotherapy vaccine from her team.

Meet Dr. Nicola Mason

Dr. Nicola Mason, BVetMed, PhD, DACVIM, FRCVS, is a professor of Professor of Medicine and Pathobiology at the University of Pennsylvania School of Veterinary Medicine. She a leading researcher in the field of veterinary immunotherapy.

Dr. Mason has pioneered groundbreaking cancer treatments for dogs, including immunotherapies that activate the body’s own immune system to fight osteosarcoma.

Her current research focuses on innovative cellular therapies, including CAR iNKT cell treatments designed to target metastatic disease. Dr. Mason’s work is helping shape the future of cancer care for both pets and people.

Resources Mentioned in This Tripawd Talk Episode #130

Connect & Learn More from the Tripawds Community

Transcript: Hope for Osteosarcoma in Dogs with Immunotherapy from Dr. Nicola Mason on Tripawd Talk Radio #130

TRIPAWDS: Dr. Mason, I am so excited to have you on our show today. Thank you for making time to be here.

DR. MASON: Thank you. I’m super excited to do this. I really am. And I do want to just say, before we start, that the work that you do with Tripawds is amazing. And it’s really important. You know, I speak to a lot of people who are trying to sort of make that tough decision about amputating their dog’s legs when they’ve been diagnosed with bone cancer. and you know, often I’ll refer them to your website, or they’ve already seen it. 

You know it really makes a difference to people to sort of see that there’s sort of life after amputation, if you like, and that tripods do very, very well. So it really makes a big difference, and as you and I both know you know, some of those dogs do go on, and do very well with their long-term prognosis. So thank you. Thank you for the work you do.

Who is Dr. Mason? And How is Her Work Making a Difference in Pet Cancer Breakthroughs?

TRIPAWDS: Oh, my gosh! That is such an honor! I wish everybody here could see me, like I’m just so excited! I’ve been following your work for years, and you have made such a difference. And at Tripawds we’re always thrilled when we hear about new studies, because we know that there is progress being made with cancer in dogs and cats, and especially osteosarcoma, which I know you tend to focus a lot of your work on. 

I want to back up a little bit, though, and tell everybody a little bit about you, because I know who you are, but I’m not sure our audience does. You’re behind the scenes a little bit, but you’ve also been in a PBS special recently, and you’ve been interviewed by Anderson Cooper! And this is all because of the amazing work you do. 

So if you could just give a little backstory on how you’ve made an impact in the veterinary world, that’d be great.

DR. MASON: Gosh, yes, I mean, I’ve been very fortunate. So my background is actually as an internist. I’m not an oncologist, I’m actually an internist. And during my residency, my internal medicine residency, I became interested in the immune system. And it was mostly because I was seeing a lot of dogs with a disease called Immune Mediated Hemolytic Anemia (IMHA), which is where your immune system decides that your red blood cells should be destroyed.

And so you have this immune mediated destruction of your red blood cells, and I became very interested in that. After my residency, I did a Phd. in Immunology, so I could better understand why the immune system goes wrong and suddenly starts to target your own tissues, which is autoimmune disease.

DR. MASON: I did my Ph.d in basic T-cell biology and understanding the immune system. And then I did my postdoc with Carl June, who is very well known in the field of immunotherapy. And so now, knowing a little bit more about the immune system, I recognized, as many others do, that you can actually use the immune system to do things like target tissues, but not your own healthy tissues.

You can actually get the immune system to target tumors, and you can start to manipulate the immune system and augment it so that it will actually recognize tumors and eliminate them. 

This is what immunotherapy is: using your immune system to actually go and target, and kill cancer.

I came full circle from “Oh, gosh, no, we don’t want the immune system to target our own tissues, that’s bad.” But if our own tissues happen to be tumor cells, then that could be very good.

I was very fortunate to do my postdoctoral fellowship with Carl June at the medical school here at Penn, and he is an extremely well-known cancer immunotherapist, immunotherapy guy and bridging out into other diseases in addition to cancer now.

That’s really where we started. He was very keen on sort of promoting, evaluating these types of therapies, not just in mice, where we have to give mice the disease, and then see if the immunotherapy works, but actually in patients.

And of course, you know I have my patients, my dog patients who are desperate for new treatments.

Here we have very, very cutting edge therapies that are sort of one step off the human clinics.

We can evaluate those in canine patients, not research dogs. That’s important: canine patients that have the disease.

This is really how I started to get involved in finding ways to manipulate the immune system, to kill cancer and hopefully provide better outcomes, safer and better outcomes for our dogs that have these diseases.

TRIPAWDS: That makes so much sense. Now I understand a little bit more about your background, and how you got into this world. Now I first heard about you many years ago, when a dog named Dexter joined our community and was doing well. We have blogged about him so many times, and I’ll put a link to the show notes. But he was one of the earliest dogs that we saw who was living longer after being diagnosed and losing a leg to osteosarcoma.

Would you say that was one of the earliest (long-term survivors)? Forgive me if I’m incorrect. But maybe the year was, what year did he start seeing you? 

DR. MASON: 2013? I think he was diagnosed in December of 2013, and then he was amputated and had his chemotherapy, and then he had the immunotherapy. After that, what we call standard of care, so I think we treated him it was either 2013, or 2014, so a decade ago.

TRIPAWDS: Yes, and that’s about when we started to see “Hey, there is something to this medicine!” There is something to these treatments, and so we’re very excited to see how dogs like Dexter have been doing well. And unfortunately it’s not a large group of dogs that get to do that.

What percentage of dogs respond to these kinds of immunotherapy treatments?

DR. MASON: So, you know, it’s difficult to say, because there’s a number of different immunotherapies out there now. Immunotherapy is using the immune system to treat the cancer, and there’s a number of ways that you can manipulate it. So it’s an umbrella term.

But certainly when we looked at the Listeria vaccine, which is what Dexter had, the response rate there was really very high.

I think we did 15 or 18 dogs, something like that, and at least half of them went on to do really very well. So, for example, Dexter did extremely well. I think Dexter lived for 6 or 7 years.

TRIPAWDS: About 7 and a half, I think.

DR. MASON: Yeah, that’s right. Then we had another dog, Casey. She was diagnosed when she was two with Osteosarcoma, and she died when she was 14.

TRIPAWDS: Wow!

DR. MASON: Then we had others as well who lived for a number of years. Scooby Doo came from Nantucket. He died when I think he was about 15, and I think he was diagnosed when he was about nine. 

These dogs all stick out in your mind, because it’s so remarkable to see them. They keep coming back!

And it was like, “Wait, hang on, what’s going on?” So that sort of realization that something was happening, it wasn’t a sudden sort of Eureka moment. It was like, “Hang on a moment! And one or 2 dogs do well?” But this was really a much higher proportion and they just seemed to keep coming back. So it was clear something was happening. 

We did a larger trial through the COTC, which is the Comparative Oncology Trials Consortium at the NCI (National Cancer Institute) led by Amy Leblanc. That was about 18 dogs, and it was done at multiple sites across the country.

DR. MASON: So the same idea: amputation, chemotherapy, which is standard of care for these dogs, and then we followed up with a vaccine.

We compared those dogs to a historical group which is always a little bit not great. You want to do the two together and randomize them. But that was the way the study was designed.

And in that study, when we looked at disease-free interval and overall survival, we did not see an improvement which was very different to what we had seen when we did the study just at Penn, so it was certainly disappointing. 

But what we learned from that study was very, very important.

What we learned is that when we looked at the dogs that had the three vaccines (we were only giving three vaccines after amputation and chemotherapy), and when you give this vaccine, which is a bacteria, when you give it intravenously, if you get live bacteria into your body, your body’s like “Whoa! What just happened?!” and your body temperature goes up. You don’t feel very well. You can feel a bit nauseous, and then it sort of goes away. So by six or seven o’clock on the same day that they got the vaccine in the morning, these dogs felt fine, and they went home.

DR. MASON: But what we found is when we looked retrospectively at those dogs that had gone on to do really well, and compared them with dogs that had exactly the same treatment, but didn’t do well. We found that at the time of giving the vaccine, those dogs that had a big temperature didn’t feel well, you know, for a few hours after the vaccine those dogs went on and did very well.

But the dogs that when we injected them with the vaccine, really their temperature did not change very much, they seemed to feel fine. You know it was as if we hadn’t done anything to them. Those dogs did not do very well, and there was a clear distinction between the two. 

What this told us is that there was a group of dogs that were able to immunologically respond to the vaccine, right?

Just like you or I get a vaccine. Sometimes we have a fever. We feel achy. We don’t feel well. That’s because your immune system is getting activated. And there’s lots of proteins called cytokines going round, and you don’t feel very well. That is because your immune system is getting activated. And that’s exactly what we’re trying to do! 

There was a group of dogs whose bodies were responding to that immunological stimulus.

Their temperature was going up. They didn’t feel very well, and then it all subsided, and they went home. Versus the dogs, who just seemed unable to respond. Their temperature didn’t go up, they didn’t feel unwell. They sort of felt fine. So this sort of told us that the fitness, what we’re calling the fitness of your immune system, is really quite important.

If you are able to respond, if your body is able to respond to that immune stimulus, then you tended to do better. And if your body was not able to respond, then you tended to do not very well.

DR. MASON: That was really what we learned, and it was really very important. We looked at a number of different immunological parameters, and that confirmed that the group that did very well had high levels of these proteins, these cytokines.

We could see their T-cells were getting all activated, compared to the group that didn’t do very well where really nothing was happening.

So the conclusion really was, if you have a “fit” immune system (and we really don’t know what that means), and you are able to respond to some sort of immunological stimulus, you can go on and do better, and you have a prolonged survival.

So stimulating an immune system that is able to respond is one way, we think that we can have a good shot at controlling osteosarcoma. There’s lots of nuances there that we have to further discover, but it was a very important finding.

TRIPAWDS: Wow! Thank you for explaining that so well, that makes a lot of sense in my mind as a non-veterinary professional.

So is this where the research is headed now? And does this have anything to do with your latest study which we want to talk about today?

DR. MASON: Well, yes, it does, in fact. So really, what I’ve just said is that you have some dogs whose immune systems are capable of responding. They’re fit, they’re active, they’re healthy. Then you have other dogs that don’t have a very fit or active immune system.

And one type of immune therapy that is receiving a lot of attention now in the human world is something called “CAR T-cells.” Car, like an automobile car. But the CAR stands for Chimeric Antigen Receptor.

But basically the concept is that:

• You take these T-cells, these killer immune cells from the patient. You take them out of the body through a blood draw and you give them a receptor–what we do is we insert it into the cells.
• Now the T-cells have this receptor on their surface that they didn’t have before. And that receptor enables them to go after cells that have a particular protein on their surface.
• That protein is something that is expressed by a number of patients with osteosarcoma. This is called CAR T-cell therapy.
• We put these receptors into T cells and then we put them back into the patient.
• The T cell goes in. It circulates around and it’s looking for its target. So when it finds its target, it will engage with that little receptor on the surface and it will activate that T-cell, and that T cell will divide.
• Now you’ve got two that have the receptors on the surface and they will become activated. They will proliferate. So now we have four, eight, and so forth, and they will kill those target tumor cells. 

This has been incredibly effective in blood cancers, hematological malignancies like leukemia and lymphoma in people. And now, of course, we’re looking at it in osteosarcoma.

The difference here, however, goes back to that concept of what happens if you don’t have very good T-cells. And this is a problem, because the drug in CAR T-cell therapy is your own T-cells! It’s your own T-cells that we engineer to express this receptor.

So if you don’t have very good T-cells, you’re not going to have a very good drug. And you’re probably not going to do very well.

DR. MASON: This new study that we have is; we’re using a very different type of T-cells. And there’s not a huge amount known about them, and they’re called Invariant Natural Killer T-cells.

The beauty of these T-cells, is you can actually take them from one patient or one healthy donor and put them into another without them causing problems, something called Graft Versus Host Disease, without them causing problems in the recipient. Also, they tend not to be rejected by the recipient.

This is basically what we’re looking at now: taking these Invariant Natural Killer T-cells.

They’re a type of T cell from healthy, robust dogs that we have tested all the way down to single cell RNA, sequencing so very, very deep molecular dissection of the capabilities of these cells from a lot of different donor dogs.

We’ve been able to select a donor dog who’s got really good, strong, robust NKT-cells, and we’ve been able to take cells from that donor dog. Put the receptor in just like we did with the T-cells. But the difference now is that we know that those are really healthy good cells, and we have them banked in the freezer. 

DR. MASON: Basically, when a patient comes along, we don’t have to take blood from that patient and make a product for that patient, which could be a very good product. Or, it could be a very bad product, depending on how fit that patient’s immune system is.

So when a patient now comes in with metastatic osteosarcoma, we will screen that patient for eligibility, and then we can go to the freezer, take out our cells, and give them to the patient and try to work it out. If that is then able to, they go all around the body of the patient, identify the cancer cells and eliminate them.

So that’s in a nutshell, what we’re up to!

TRIPAWDS: Wow! Okay. “Donor dogs…” I know people are wondering, where do they come from?

DR. MASON: Right? Exactly so. We have screened donor dogs from faculty and from staff to see if there’s a good donor dog. We have a couple of blood donors that are here to donate blood, and we’ve screened those as well. And one of those dogs is the dog that has really good INK T-cells.

And the other thing to mention here is one of the things with these INK T-cells is, they have incredible proliferative capabilities. So we can do one blood draw from Brandy, and that will generate in the lab enough product to treat 15 dogs! Just from a single blood draw.

DR. MASON: So these are very good cells. As I said, they’ve been evaluated in a number of different immunological assays that we do in the lab and out of all the dogs that we’ve tested, this dog has some really good INK T-cells.

The idea is to have what’s called “Off-the-Shelf,” so you don’t have to make it from each patient; you can go and take it off the shelf. 

So, “off-the-shelf cellular therapy.” These are cells living therapy that will go into the patients, and they have been genetically engineered to express this particular receptor that will target, we hope, the metastatic lesions that are present in the patient’s chest.

That’s something that is a huge need both in canines with osteosarcoma, and also in children with osteosarcoma as well.

TRIPAWDS: Oh, yeah, we know about that here. And that was going to be my next question.

So a dog with lung metastasis can come in for this study and get these cells injected, and see if this actually works to get rid of the metastasis or manage it?

DR. MASON: We don’t know, we’re certainly aiming to get rid of it. But I think we have to manage expectations right? And you know it’s a clinical trial, which means, we don’t know if it’s going to work. That’s why we’re trying it.

We have treated our first patient, Rex, a beautiful dog. The first thing that we need to show is that it’s safe, right? So genetically engineered cells from a different dog going into a different dog. First of all, we need to show it’s safe. And that the treatment was safe.

He started off with the lowest dose. And this is a Dose Escalation Study, so the next dog will receive a higher dose. And if the next dog is okay, we’ll receive a higher dose again. That’s what we call a Dose Escalation Study.

DR. MASON: What we learned from Rex is that the dose that he received was completely safe. He didn’t miss a beat, you know. His owner was very in tune with him and sort of said, “You know, he actually seems peppier. We’re walking around the block a little bit more,” and so on.

But his disease did progress, and sadly he passed away, after about two-and-a-half months from progressive disease. But I think again, what is really important is when these patients come to us, you know, is managing expectations.

We don’t know if this is going to work. We don’t know if it’s going to be safe. But we learned that now, you know. Now, one patient did receive those cells, and it was safe for him at that dose, which was a very low dose.

It didn’t really control his disease. But now we have a little bit more confidence that we can go up to a higher level, and maybe with a higher dose, we could actually control his disease. So we learn all the time.

This is why these trials have fairly tight criteria. You know it’s not that we can just treat everybody, because what is important is that we can make progress, and we can learn.

The people who come and bring their dogs onto the trial are sort of really very aware of that, and they become part of our team to be honest with you. They give us reports, and “He’s doing this or I’ve noticed this and that.”

And together I truly believe that when we work together with people who have to cope with this terrible diagnosis for their dogs, and people in the clinics and people in the research lab, everybody coming together, we are making progress.

Maybe it’s not the “It works! Everything’s great!” but we learn, and that allows us to make progress and bring these things forward. So it’s really very, very important. And I think it’s good for people, it gives people hope that maybe it could work.

It also gives people, I think, a sense of taking back control, right? And this hopelessness of “Nothing’s going to work.” Now you’ve got a shot at it, and you feel that at least you’re going to try and fight it.

I think that that empowers people and also clearly obviously helps us very much with the research.

And of course, to see these dogs coming back through the door every time with the Listeria vaccine when they really shouldn’t be, is an incredible, incredible thing.

TRIPAWDS: Yes, you know people who do these clinical trials, who volunteer, and especially somebody like Rex’s parents, that is so courageous and says so much about their willingness to go forward and help other dogs.

DR. MASON: Yes.

TRIPAWDS: They put their grief aside. Because, you know, when you get an osteosarcoma diagnosis that’s really a terrible diagnosis. And then when you get hit with lung mets, it’s like getting that news all over again. But they put their grief aside and say, “We want to do this! We don’t know if it’ll work, but we’re going to try.” I love that! Those are some really special people.

DR. MASON: Yes!

TRIPAWDS:. I love the work that you’re doing, and this clinical trial. At what point do you think it’ll be wrapped up, and you’ll know whether or not it actually worked?

DR. MASON: So the 1st study is for dogs with lung meds, and we’re aiming to enroll around 15 to 18 dogs. So it’s a small study, obviously. It depends how quickly we enroll them, as to when we’ll get the results. But we are already learning. And we’ve learned a lot from Rex.

So I would hope–this is a study, by the way, that’s funded by the National Cancer Institute–and you know, they’re funding it, because the concept, of course, is to assess safety and efficacy in the dogs before it goes into children. And that’s how we can do these studies, because, we have a significant amount of money from the National Cancer Institute.

These studies are not cheap, and the therapy and the clinical trial is all paid for. So there’s really no cost to the owner other than they have to travel here and have to be here for all the visits. So it really is something that’s helping us obviously in the dogs and also helping us for the kids as well.

I would imagine, in sort of two years we should have sort of really analyzed these dogs, and have a good idea of what these cells really did. Where did they go? What did they do when they got there? You know? How did they work? Or why did they not work? And what can we do to make them work?

Then we have a second trial with the same cells. But this will be in dogs that have just been diagnosed. So this will be, they will be just diagnosed, they’ll come in and they will get these cells before they get amputated. And then what we’re able to do then is, we’re able to look at the primary tumor, the tumor that’s in the leg, and see if these cells went there.

And then we have some very advanced imaging where we can look to see what the cells did when they got there. Did they attack the tumor cells? Did they modify the environment of the tumor? And of course, we want to determine whether giving those cells prior to amputation actually results in longer disease-free interval.

 Because once those cells are in there, they’re in there, and it’s not like a drug, that you give the drug, and it gets metabolized and its levels go down. Quite the contrary. When the cells go in there, the idea is that they’ll actually expand and they’ll go up eventually. The idea is that they calm down once all the tumor has gone. 

These are all questions that we need to ask and answer, and it will help us go to the next stage. So that’s another trial that’s going to be starting, I would imagine, probably in the next six months or so.

TRIPAWDS: People who have a dog with metastases, is there a certain criteria for the size of metastasis? Are you looking for one met? A lot of mets?

DR. MASON: No, the dogs have to have a sort of an expected life expectancy of two months, so the earlier we can get them with the metastases the better, and the more likely it is that the therapy will work. If the metastases are smaller, it’s hard to sort of treat a big solid lump in there. So earlier metastases is clearly better.

We screen the primary tumor, we go to the pathology IDEX and whoever looked at the original histopathology. We go back in time, and we look at that to make sure the target of the engineered cells is present. We screen the tumor to give us an idea of whether that target is present. That’s another eligibility criteria. 

And then they have to be well in all other respects. So dogs without any what we call comorbid morbidity, so no sort of  liver disease or kidney disease or other things, you know that they’re trying to manage.

So, healthy in all other respects, and who have undergone amputation and chemotherapy, and now have developed metastatic disease. So that’s who we’re looking for. 

We have our trial advertised on the AVMA Clinical Trials website. We also have it advertised on the UPENN Comparative Immunotherapy program website as well, so you can sort of see it in a number of different places.

TRIPAWDS: We have it on the Tripawds website, too!

DR. MASON: You can just give us a call, and we’re happy to chat and see if the patient sounds as though the trial would be a good fit, and if so, then we organize them coming in for screening, and we go from there.

TRIPAWDS: Alrighty! And there is a pre-screening survey that you have available that people can take right now, and we’ll share all these links in our show notes. 

But I would say, you know, if I was in this situation right now, I would do this in a heartbeat, and at least take the survey to find out if your dog is eligible.

This is so exciting and just hopeful! When I think of the work that you do, I just see the word “HOPE” because, like you said, right now we don’t have the answers. But we’re getting there. We’re getting such a better understanding of this really terrible disease in dogs, cats, and people, of course. So thank you, Dr. Mason, we really appreciate you being here and explaining everything. You made it so simple for us.

DR. MASON: No, I super appreciate it! I appreciate everything that you do. Thank you for the opportunity to get the word out. Really, do appreciate that, and maybe in a few years time I’ll come back and hopefully tell you about the results of the study.

TRIPAWDS: Yes, we will! We will be keeping an eye on it, and we will be watching all of the great work that you do. Thank you so much.

DR. MASON: Thank you, thanks very much. Bye, bye.

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