Dr. Impellizeri: Because from there I expanded the use to not only immunotherapies but also targeted electrochemotherapy, where now, while we’re opening the cell membrane, I can deliver chemotherapy directly to where I want it to go. Longer term survivals, minimal to no side effects, happier pet parents, happier owners and something that also is complementary to our standard of care.

Dr. Venable: Hello and welcome to the Veterinary Cancer Pioneers podcast. I’m your host, Dr. Rachel Venable. And today I have a real pioneer with me, Dr. Joseph Impellizeri. He is a pioneer in electro chemotherapy, and he’s really been educating a lot of us, myself included, about this new therapy. And he has lectured all over the country internationally. He’s actually authored the first textbook on veterinary electroporation, and he leads the Barrymore Center for Advanced Cancer Care with veterinary oncology services. And so I’m so excited today to really learn more about this therapy, how we can use it, when to use it, and just more about his story in general. So doctor, and thank you so much for being on the podcast with us today.

Dr. Impellizeri: Thank you so much for having me here.

Dr. Venable: So I always want to get a little more information about everyone and just start at the beginning. What got you into veterinary medicine or certainly veterinary oncology.

Dr. Impellizeri: So it’s a great question, and it still makes me laugh to this day. I always had an affinity for medicine. I always had an affinity for health care. And when I was younger, I saw an injured squirrel that I ended up rescuing when I was in high school. And that just tips the scale. And I knew I wanted to do veterinary medicine at that time.

And still it is such a difficult field to get into. That I basically said if I do not get into veterinary school, maybe I’ll just default to medical school. But fortunately, I was accepted and the rest is history. While I was in school, I was very much into doing everything. Surgery, neurology, internal medicine, dermatology, everything, ophthalmology, just to learn as much as I could. And then I realized after I was practicing for about five years, that I wanted something a little bit more and gravitated towards oncology. I felt it was more one of hope than of despair. And my career has basically been met with what else can we do? What else is out there? What other options exist? Who’s doing something more advanced on the human side that we can bring to the veterinary side? And that’s really what’s been driving me for now 30 years, a passion of trying to improve upon what we’ve been doing thus far, and how to really get cancer shut down in a kinder way that it doesn’t hurt or affect the patient being treated.

Dr. Venable: Oh, that’s. Yeah, because cancer often a lot of times people will talk about how the therapy may be worse than the disease itself. You hear that a lot, especially in people. So what have you found that, trying to be a better type of treatment?

Dr. Impellizeri: So I think when I first started in the field, the first 2 or 3 years was really the standard of care and pretty much predominantly either surgery to remove it and then follow with chemo. Radiation was just emerging at the time and wasn’t very readily available. And as I started to become more, a little frustrated with the outcomes with those protocols, I started looking for what else we could be tapping into. And I was fortunate many years ago, almost 15 years now, to have a client who really was interested in a specific type of cancer vaccine, a cancer vaccine that was delivered using this concept of what’s called electroporation, using an electric pulse to have a transient opening in the cell membrane and allowing delivery of that immunotherapy. And I said to her, Iryna, there’s no way we’re going to get this. It’s in Europe. There’s so much red tape. And she was persistent and we ended up getting it. And the rest, as they say, is history. Because from there I expanded the use to not only immunotherapies but also targeted electrochemotherapy, where now, while we’re opening the cell membrane, I can deliver chemotherapy directly to where I want it to go. And that type of technology, which is much more mainstream overseas, is truly emerging here, not only on the human side but on the veterinary side as well. The concept of this electroporation based cancer therapies with targeted electro chemotherapy being predominantly for local disease, controlling the tor locally, and the immunotherapy, what they call gene electrode transfer, the opening of the membrane to deliver a plasmid intracellular has really tremendously changed our ability to have longer term survivals, minimal to no side effects, happier pet parents, happier owners and something that also is complementary to our standard of care.

Dr. Venable: For the gene transfer that you’re talking about that I’m not as familiar with. Is that something that’s commercially available? 

Dr. Impellizeri: Unfortunately not yet. So gene electrode transfer is using an electrical pulse to actually allow a transient opening to deliver an immunotherapy. In the case of what we’ve been doing for many years, we open a cell membrane in a lower leg muscle to allow a muscular expression of a systemic immune response. So if you think about the average, injected into the muscle, intramuscular, injected into under the skin, all of those immunotherapy pathways are still based on the antigen with gene electrode transfer, you're bypassing it and you’re providing an intracellular delivery.

And that delivery changes the immune response by up to 100 fold. The downside to the technology is it does require a short sedation. So people will say do you have to sedate them in people. They use local anesthesia for this. But in animals I think that little bit of a, if you will, a pinch or something, it’s just a quick procedure, but I think it needs a short, short sedation. So that’s been a disadvantage that we’ve been trying to look at other options for delivery systems. But so far gene electrode transfer has really risen to the top. And until we can find a better choice, that’s going to be the mainstay of our cancer immunotherapy delivery.

Dr. Venable: That’s really interesting. And focusing over onto the electro chemotherapy since more of us have that option available and hearing a lot more about that. When do you decide that a case is a good case for electro chemotherapy versus other treatment options, or do you combine it with a lot of things?

Dr. Impellizeri: Yeah, it’s an excellent question. I think the hallmark of effective cancer therapy is combination therapy. So very much I tried to bring other modalities surgery, chemo, radiation in with targeted electro chemo as much as possible. But realistically, the cases that we get are probably twofold. The first is, hey, I removed this tumor, but I couldn’t get it at all, and now we’re looking for something else to control local recurrence. And so for the most part, that falls into, hey, let’s cut out more tissue, which is not always possible. Let’s consider radiation therapy, which has its ups and downs in terms of availability and cost and potential side effects, and finally, targeted electro chemotherapy, which most scar lines are treated as a single treatment. So that’s the first area that I think we’ve been using predominantly. 

The second is looking at non respectable tumors and an owner that says, look my dog has a tumor of the lower jaw. They’re offering an option to remove part of the lower jaw. I don’t want to do that. What else can we do? And then we look at things where radiation plays a role. And obviously is there a role for targeted electro chemotherapy. There are very, very few tumors that I can’t tell you. I can find a role for it. But I’m also very, very clear with the owners to make sure that I present them every option that exists. I think that’s the right way to do this. And even though you may have a specialty in this technology, I sometimes have to tell owners I don’t think we’re doing it for the right reasons. I think we need to reconsider or I really think you should do radiation here. The data is far more compelling to pursue that modality and not the targeted electrochemo.

Dr. Venable: So you’re calling it targeted electro chemo. Why are you using that phrase otherwise? I’ve just heard it as electro chemo.

Dr. Impellizeri: Yup, no, absolutely. So when it first originated about 40 years ago, out of France, the name was simply electroporation with chemotherapy, and then it shortened to just electro chemotherapy. And I found over many years when I use that term, owners still think of it as shock therapy. “Oh, electro, what are you doing? You’re shocking. my animal.”

And it’s nothing like that. So I’ve effectively decided to change the nomenclature to define it as targeted electro chemotherapy. And it’s become far more acceptable, especially trying to describe it to owners. The joke we used to say is, “Electro chemotherapy. Are you trying to reanimate Frankenstein’s monster? What are you doing to my dog?” And you have to break it down and explain it. But when I say it is targeted electro chemotherapy, they like the fact that it’s very focused. The fact that you’re not just hitting everything and hoping for some of the damage to be to the cancer, and it’s made a difference, in my opinion. So for us, we tend to call it targeted electro chemotherapy. The genre would clearly define it still as electro chemotherapy.

Dr. Venable: But that certainly makes sense to me because I’ve definitely had clients that were imagining more of the Frankenstein situation. And so trying to explain to them, it’s not this is just if the two were. So it is funny what can come to your imagination. And a lot of people, they haven’t seen electro chemotherapy. So can you walk us through what that typically looks like ? How does that procedure walk us through the step?

Dr. Impellizeri: So initially we do our consults and confirm that the patient is a good candidate. We make sure that their staging is clear and we know what we’re focusing on. We explain the risks, which are truly minimal. This is a non-thermal technology and with the exception of some redness or irritation at the site being “treated,” we really don’t even see any type of pain or discomfort on the way home. It’s also an outpatient procedure and again a very short anesthetic protocol, typically up and down I’d say within 20 minutes. So the patient is prepped and I.V. catheters placed. We then induce the patient with a short term anesthetic depending on what we’re treating, we may or may not intubate. If we intubate, we have the tube placed, and then they’re placed at least on oxygen. Essentially, the area being treated is usually clipped and prepped, but not always. Some of the areas are very sensitive, and clipping at the site will end up causing more irritation post procedure. So it’s a little bit of a judgment call when it comes to the clip in prep, but we want the area to be clean and well defined. Essentially, then once you have the patient prepped, you administer intravenously, usually the chemotherapy drug. bleomycin. Bleomycin is a fairly innocuous chemo at a very low dose and that goes intravenous. 

We wait about 7 to 8 minutes. And the machines we have actually have a timer. So as soon as my team is injecting the drug, we hit the play timer and it counts down at about seven minutes. We then apply the electrode to the tor. Now the electrodes vary and depending on the different machines, they can sometimes be very, very advanced and sometimes a bit medieval. The electrodes we use are typically a small array of linear needles in a linear pattern of about eight needles, four per row. And with that electrode we have different sizes: a centimeter, two centimeters, and actually up to 3.5cm. So depending on the depth of the tumor, I have the ability to modify how deep I want to insert the needles to get a full encompassing of the area to be treated, including the perimeter. The electrode is then placed into the tumor. The machine is charged. We call it arming and then treating. At the treating the pulse goes through, depending on the area being treated. If there’s any type of muscle, you may get a contraction, and if there’s no muscle, then typically it’s just a no nothing at all to the patient, no movement or anything. Contraction is usually mild as a quick little tone of muscle change. But other than that, depending on the machine, you can treat it again within a couple of seconds. Some machines take a little longer to reset, but essentially what you’re doing is you’re taking that electrode and you’re going around the tumor and into the tumor, and you’re trying to make sure that you’re covering the entire region, including possibly a section of tissue which would be considered normal.

We know that many of our tumors, soft tissue sarcomas and mast cell tumors, have tentacles that extend beyond just what the visual side of the tumor looks . And trying to make sure that we’re encompassing a wide area of treatment can be crucial for maintaining local control. Once the patient is treated, we rarely see any type of bleeding. There is something called the vascular lock, which tends to cause an attenuation of attrition of the smaller blood vessels, so it rarely ends up being a bleeding post procedure/treatment. Occasionally, sometimes mast cells will not behave so well, but once the treatment is done, the area is just cleaned. We make sure there’s no bleeding and then the patient moves into recovery.

And recovery is very quick and typically they’re up and nothing happened. I usually tell owners 24 to 48 hours, look for some redness or irritation, but usually the redness and irritation doesn’t even correlate to the patient’s status, meaning the patient’s doing great. It may look a little more red and irritated than you would expect for certain skin tumors, cutaneous tumors. That’s the general uniqueness of what’s being done. We’ve expanded upon our ability to treat other sites and currently the two most advanced options are bone and nasal. So where the electrodes for skin are usually needle based, electrodes, very, very small, very, very sharp and not really very traumatic. But the electrodes that we’re now using for feline oral squamous cell carcinoma involving bone and those tumors involving the nasal cavity are a blunt BIC pen and probably about half that diameter.

And we’re able to go into the area that we’re treating at the end of that electrode. That’s where the actual release of energy occurs. So figure about a centimeter in. Figure that energy that’s released is, so at the end of this linear single probe you have a sphere figure a blow up of a small balloon at the end. That’s your electric field. And then knowing that you can move this electrode in and out of the cavity you’re treating in the nasal cavity, these are dolichocephalic dogs, the long nose dogs, they take longer because we’re going in and out of both sides of the nasal cavity to cover all areas. For the most part, the oral squamous cell carcinoma is in the cat. As long as I can see some type of opening on an oral exam, then usually I have one, maybe two treatments and we’ve started to see some early positive effects. So I’m excited about that because as you know, that is a cancer that we have not been able to make a difference on for years, for decades. And if we can try to find something that can improve survival and control, that’s wonderful.

The technology for that stems from human data for metastatic lesions of bone. So their cancer has metastasized to bone. It’s very painful. They’re extremely uncomfortable. And they started to look at roles for electroporation based. There have been bone-based cancers. And they found that once they treat in an identical way, these clients have almost a complete resolution of their bone pain, which is unbelievable. So we’re looking to expand upon that and currently trying to do more and more cases to see if we can make a difference. I have four currently. I’d say three out of four, I’m still just wow, I can’t believe that they are doing so well. I had one that was not doing so well and I thought that was going to be a failure, and she just emailed us the other day and said, hey, we’re still doing okay. Can we consider more? So I think we’re at an early stage of doing something more groundbreaking. And for me, that’s very, very exciting and drives me in terms of passion to improve upon current therapies.

Dr. Venable: And that would be amazing if you could get something to work for oral squamous. That’s such a frustrating disease. So yes, I would love to see what you guys find. And my other question though, is I’ve always heard that electro chemo doesn’t work very well for bone. So do you have to have specific probes or a specific machine for these situations, or could any machine work because you said, I thought you weren’t really supposed to do both.

Dr. Impellizeri: Yes. No. Great question. And I think it’s something that needs to be clarified. The reason for the lack of use of bone with electroporation-based therapies is because the needle electrodes were unable to penetrate into bone. The newer electrodes are there, almost like a bone marrow where you could actually make a small hole if needed and bring this blunted linear probe into the center of the bone. So the combination of the newer electrodes and having a generator that can do that can actually push the voltage that’s needed for bone electroporation. So it’s a little bit of both when it comes to why you can or cannot treat bone based tumors with targeted electro chemotherapy.

Dr. Venable: Yeah. That’s interesting. So do you have to actually make a hole to put the probe in or.

Dr. Impellizeri: In tumors that have no lytic opening. Right. There’s no connection. Sometimes you get those osteosarcoma that are fairly focal and you really have no way of getting in. In that case, you do have the ability to refine into the bone. And we all know the risks of trying to go into bone that’s already damaged and abnormal, in terms of pathologic fracture. I have not had to do that yet. Most of the oral tumors that we’re seeing, I usually can find an entrance point within the oral cavity, so I don’t have to make any type of tunnel, if you will, to get access to the area.

Dr. Venable: And speaking about oral tumors, and these animals are under anesthesia. So they’re getting oxygen and we’re using electricity. I mean, does that ever scare you? Have you ever run into an issue? Do we need to be extra cautious?

Dr. Impellizeri: No, I think because we’re not creating a spark. And it is a non thermal technique. The use of targeted electro chemotherapy in oral cavities especially with oxygen flowing. We have not been met with anything of concern. The things they’re finding on the human side is that when you provide that pulse anywhere near the heart you may run into some EKG abnormalities.

So on the human side, they actually gave the EKG to the delivery of the pulse. For our experience and treating many tumors on and near the heart, I have not had any concerns, no EKG abnormalities. So we’ll keep an eye on things overall.

Dr. Venable: That’s really interesting, but it makes sense with the heart. I hadn’t thought of that, but that does make a lot of sense. And so, are there any tumors that you can that just come to mind that you would say electro-chemo is not a good option for?

Dr. Impellizeri: Really I think the reason you would not do it is because of comorbidities. Right? This dog is battling severe DJD and can't even get up. What are we doing here? And I think just accessibility. So we’ve treated just about everywhere including bladder, brain, prostate, we’ve treated everywhere. I think that the mainstay of the therapy is going to be cutaneous tumors, scars, oral tumors.

But we are starting to see options exist for internal tumors. And whether we approach that laparoscopically or through an open exploratory, I do think that that’s becoming much more of interest. On the human side, there is very compelling data for hepatocellular carcinoma. I mean, really, really good studies that have come out. The difference between the ones we deal with in the dog is by the time we see them, they’re fairly massive, whereas on the human side they can still be small, but multiple.

So I think that’s another area that we have to look at the technology and figure out if there is some way we can improve upon it. So I’ll give you an example. The electrodes that we currently use 90% of the time are linear electrodes and essentially have an extension of about half a centimeter to a centimeter deep to the needle of where I place it. But there are hexagonal electrodes. So instead of having a linear array, these are hexagonal arrays. And they produce far more energy and far more depth. So we’re starting to look at more hexagonal electrodes in tumors that are greater than, say, two centimeters. And starting to see better responses. So I think all of this is all still in development, but we try to take a look at what’s being used on the human side. And then from there extrapolate to how we can use it on the veterinary side. 

Dr. Venable: Right, that’s really interesting to think about bladder tumors and brain tumors. How did you even access the bladder or brain, was that laparoscopic? At least for the bladder?

Dr. Impellizeri: For both of those, it was with a surgeon. The surgeon got us in. So the brain was a complete exposure. And there was nothing that could be done for this dog, no radiation. And so they wanted to try that. And we did. And the dog recovered and did okay. But I’m not quite sure of the long term success with that one. The bladder one is met with some of our colleagues down in South America who’ve been doing bladder targeted electro chemo for probably five years, and they have some very good data that basically get me into the area, give me exposure to the bladder. Most of the tumors are trigonal and obviously non respectable, and they’re treating as a one and done. So single treatment go in, treat the area. And they’re seeing reduction of tor burden and obviously improvement of urinary patency which is fantastic. So we’re trying to do more of that. But it's funny we really try to educate other oncologists and tell them about this technology, which is the main group we want. But I do think that the surgeons, the neurologists, the internists should also know about this because they’re also not aware what other technologies may exist that could be a better choice. And any time there’s an emerging therapy like this, it’s always met with skepticism. And it should be. But we really try to ground clients and referring vets and other specialists with the data that exists from publications, personal experience and obviously anecdotes from those that have been doing this for some time.

Dr. Venable: That’s really interesting. I had no idea that South America was doing that, and maybe I’m just biased because I live in the US. So I feel a lot of times we’re on the forefront of things. But it sounds like with the electro chemo, everyone else is on the forefront. Am I wrong? I don’t know.

Dr. Impellizeri: I think you’re exactly right. I think this is one area where I do think the United States has been slow to catch up. And I tell owners, there’s a lot of people that once they hear about this, they end up traveling to Europe for treatment just because they like the concept. And it makes sense. Some of the larger centers, they’re doing a ton of this. There’s groups in in Italy as well that are doing this, for metastatic disease from breast cancer, areas of cutaneous basal cell, things that are just being met with no good response, facial tumors where you’re limited on how much you can truly cut out or what you can irradiate. So I think this is an area that I agree with. We’re slow to the table here. And I think that our colleagues outside the US have really been at the forefront for some time.

Dr. Venable: Speaking of just Europe and things, I know a lot of the machines, when I’ve looked at myself or talked to other colleagues about, okay, we want to start electro chemo owner practice. How do we go about buying machines? It seems a lot of the machines are overseas, and sometimes there’s even issues trying to get them in. Are all the machines the same? Are they different? How would you answer that? And then my follow up question is, how does a group go about trying to find the right machine for them?

Dr. Impellizeri: So excellent, excellent questions. And I get these questions all the time when people reach out and say, hey, I’m interested in adding electro chemo. I need your opinion, I need your this. And so this is what I tell them. The machines are very different. You would think that they’re all fundamentally the same, but they’re not. They are not. And because of that, you have machines that are more likely to cause necrosis, the dark blackening of tissue that unfortunately leads to quality of life issues to the patient. And sometimes an owner regretting that they made a decision, whereas the better machines, the higher caliber machines, we have none of that. We don’t deal with any type of necrosis. I think it’s also a matter of, you’re going to pay more, but you’re going to get more. The other thing is the electrodes, the electrodes really make or break the ability to treat. And some of the lower cost machines have electrodes, but they’re limited. And other companies have an array of electrodes that, we have one that basically slips on your finger. So you can put that into the oral cavity and get all the way down deeper into the throat in areas that normally were not accessible. So I think the important thing is knowing there are differences, except for one, I believe they’re all manufactured overseas. And then the second question is, how do we improve upon getting the right information to the right specialist about making these choices? 

One of the things we’ve been looking at, and we’re planning to do for 2026, is to actually have a forum here in the United States on electroporation based therapies and have some of the people who’ve been doing this for a long time, come lecture, almost repeat what’s being done overseas for European specialists and everything. And I think that’s going to help tremendously because that’ll be a forum for not only didactic education, but we’ll also have the ability to have clinical experience. This is how we do it. Let’s pretend, this potato is a tumor and we can treat it, which gives people the confidence before investing and making sure that they do their own due diligence to know that this is the right generator. Some of the machines I find are limited in terms of their customer support or when something goes wrong. How do I get a replacement? So those are logistical issues related to any manufacturer. But I think it’s important before you jump in to know what options exist out there. And I do think that it’s just going to be a matter of time before we have those types of educational lecture workshops that start to bring awareness to the United States, so that you do have an educated opinion in making a decision.

I hear a lot about that, so-and-so contacted us. They’re pushing us for this. What should I do? And I don’t think you should be pushed. I think it’s a great modality that should be an additional armamentarium to the existing therapies we have. But I don’t think you should go about it lightly just to add it to your practice. In Europe, there are actual classes two, three, 4 or 5 day workshop class where it’s a classroom training before you get out there and are able to treat on the human side, they’ll do the exact same thing with have a three day class where you are comfortable and understanding before you open it up on the first patient. And I really I’m trying to mimic that here in the United States. So I anticipate the fall of 2026 to be able to launch something. In the meantime, I would tell prospective interested specialists and other veterinarians, look at the company, demo the product, ask for references, ask the questions you need. What happens when this breaks? What happens when I need a question? Answer and see if the answers that are provided make you comfortable in selecting them as your choice.

Dr. Venable: I would love it if you have those forums, so certainly keep us posted because I think that would be great. In oncology we don’t have a lot of wet lab scenarios, so that would be really nice to get real hands on and work with other people. Because I know for myself that’s been something that was tricky. It’s okay, how do I educate myself on this, trying to get the training. So yeah, I would certainly be very excited if you guys do that forum. So definitely keep us posted.

Dr. Impellizeri: I will, if you think about it, with the modalities we currently have, there is no real wet lab need for anything because we haven’t had anything really traumatic to add to our options list, and this is the first time where you have something that’s more significant. And I just want to make sure that we launch it correctly, that it comes out because I really want more of our colleagues to have access to this and treat more patients. And I like to see more combinations, not only among us would say chemo, radiation, targeted electro chemo, but possibly surgery. Right. Maybe a pre-surgery treatment to control margins a little better, followed by surgery knowing you can’t get it all, and then a subsequent targeted electro chemotherapy. Those types of combinations are going to be the future. We’re going to start thinking more like a tumor board instead of just, can we cut it out?

I had a client from the Midwest. They wanted to come to us. The cat had an oral squamous cell carcinoma. Unfortunately, they went to surgery. They took off most of the jaw, put on a feeding tube, and they were trying to get to us to treat the residual disease. I don’t think it was a week and a half. And the cat progressed and I just said, here you are doing an aggressive surgery, knowing that the outcome is going to be limited. I really look forward to trying to find collaborations among specialists to say, how do we make sure that we’re doing everything? Maybe the radiation oncologist, right. Let’s have an opinion on that as we go forward. Here’s how we seek combining modalities. So I hope that becomes the standard in the next decade.

Dr. Venable: Yeah, I agree that would be nice. And yeah, those oral squamous in cats is just so rough, such a terrible disease and so devastating. I was curious about it and I don’t know if this depends on the machine, but if you’re treating a scar, do you usually do 1 or 2 treatments of electro chemo versus a big tumor? How do you decide how many treatments to do?

Dr. Impellizeri: So It’s a little bit subjective, but I usually find that for an incomplete margin, for a fairly low grade tumor, it’s a single treatment, the one and done. I’ll then recheck them, sequentially every couple of months and everything. Advise the owner what to look for because unlike radiation you can treat again there’s not a limit on what you can do with the electroporation based therapies. For the larger tumors, the bulk cancers again, a judgment call, but I usually find somewhere between 2 to 4 treatments every 2 to 4 weeks. And that’s a little vague because it really depends, right? And we also have to make sure that as we’re looking at what we’re treating with this therapy, we’re also looking at the tor and the overall behavior, right? Is this a higher grade sarcoma? In which case we should be talking to the client about additional therapies to control metastatic disease and not just focus on the one treatment. So I really try to make sure that we’ve educated the client and the referring vet about behavior, prognosis, and why we’re choosing the therapies we would be choosing at the time.

Dr. Venable: And that makes sense to me just in general. Right? I feel those should be the steps to go through with any of these cases. And one other thing I wanted to ask is that you mentioned giving bleomycin, but I know some of the older studies, or at least I believe they would give it, in the tumor or cisplatin was another one. Why have you moved to IV, or are there times that you would give it in a scar or in the tumor?

Dr. Impellizeri: There are times I would still give it intra lesions. Mostly it’s become avian and exotic. So the birds, chinchillas, rabbits, because we don’t really have dosing pharmacokinetics/pharmacodynamics of the avian or exotic species to know that the dose is correct. It’s very much an extrapolation. So for those types of avian exotics, inter-lesional, for the most part we’ve shifted to intravenous probably more because of chemo safety and minimizing exposure to the team. There are a few cases where I still will go intra-lesional, but for most of those they become few and far between compared to the intravenous approach.

Dr. Venable: When you mentioned avian and exotics, what’s the, I don’t know, craziest animal or coolest animal that you’ve ever treated with electric chemo?

Dr. Impellizeri: I’d have to say that besides the birds, the chinchillas, the rabbits, the ferrets, we were able to treat an Asian elephant at the El Paso Zoo. She had breast cancer and there was no surgical option. It was a very humbling experience. We treated her six times with the zoo team, putting her under full anesthesia each time, and it was filmed for Disney Animal. So if you are really bored and you want to see something amusing, it was very, very humbling. She was amazing. I learned a lot. I learned that the skin of an elephant has an epidermis about two centimeters, which helps protect them from the lions, but makes it difficult to get penetration. But we were able to use a different set of electrodes that had a sharper point and thicker and get the penetration we needed, and she went almost another two years before progression. But I would tell you that was an experience in itself. I think there’s going to be more exotic animal zoo animals that will benefit from this, and I’m hoping we can get the word out to let people know that this modality exists. It has value. It is not for every treatment, every patient, but you should know about it.

And at least the questions I usually get from owners. Why doesn’t my vet know about this? Or how come I didn’t know about this? And I say it’s an emerging therapy. It’s predominantly based outside the US, but it’s grounded in good science and rooted in good responses. And because of that, we’re really trying to launch it, expand upon it, educate more people here so we can have more cases to be treated because we see the value of what it provides.

Dr. Venable: And certainly seen that too, since I’ve started using it. And that is a crazy story treating an elephant. And it was on Disney. So that is pretty cool. I’ll certainly have to look that up, but I never really thought about the elephant skin. But yeah, that would be hard.

Dr. Impellizeri: Very, very difficult. I mean, I think the funny part is when I first was brought in to consult and I said, well, do you think I could get close enough to lay hands on it and everything? And they’re like, no, I think she’d probably kill you with her trunk. So they said, we’re going to use general anesthesia. And I said, I think that’s a great idea. But watching an elephant, God, she was probably 4,000 pounds, something that, to be put under general anesthesia. I give the zoo tremendous credit. They did a wonderful job and didn’t just do it once. It was a total of six times that they did it, and I could not ask for a better team to work with. A really amazing thing to see dropping such an incredible animal under anesthesia.

Dr. Venable: Right? I can only imagine that’s I mean, even just her trunk, but also her legs. If she’s laying on her side while you’re trying to treat her, you have to make sure her legs don’t accidentally take you or twitch. That would be.

Dr. Impellizeri: They had to. We had to tie her leg and put it on a hoist, and then three guys would have to pull to lift the leg out of the way so I could get to the mammary tumor underneath. So it was really and you don’t know these things until she’s under. right? So you’re doing a lot of things on the fly not knowing. And again, the team I had was second to none. And I feel very lucky that we were able to make a difference with her. And I hope that down the road, we can continue to offer this to exotic animals and owners that are looking for what options exist outside of the mainstay of what we currently offer.

Dr. Venable: I totally agree, I think this could really be used in so many different ways, and I think it’s got a lot of value to it. So I’m excited to learn more about it, be a part of it, and can’t wait to see what the future holds for all of this. Dr. Impellizeri, this has been a fantastic conversation. I love learning more about this. And as we wrap up today, I always ask everyone, who do you think would be a good guest on our show?

Dr. Impellizeri: I think first of all, Dr. Venable, thank you so much for allowing me to be here. It was wonderful, and I very much appreciate the time and the ability to try to educate more people about this technology. I think if I was going to pick somebody, I would look to find you, somebody who is doing this in a unique setting, perhaps the people doing the bladder-based targeted electro chemo to hear their perspective on it. I just think you have to find someone who is more on the cutting edge of options to really continue to move our profession forward and allow more people to think outside the box for what we can advance and improve upon. So I’d be happy to share some of those names with you at some point. But yeah, there’s a few that I think would be a very interesting podcast attendee.

Dr. Venable: Perfect. I can’t wait to learn. And yeah, I agree, the cutting edge. It’s always interesting to see where people are going, what they’re doing, what are the possibilities. So definitely excited for all that.

Dr. Impellizeri: If I could just lastly, the latest thing that we’re looking to do is with our immunotherapies, that gene electrode transfer. We’ve started adding in the PD-1 inhibitors. So having the ability to combine an immunotherapy with an immunotherapy that’s more generic, if you will, we are really starting to see some good survival times that we’re hoping will continue and when evaluated statistically will be significant. So it’s mimicking what’s happening on the human side. When you combine a PD-1 inhibitor with other therapies. And I’m really excited about that because I do think it’s now starting to offer a better chance than currently what we’ve been able to offer.

Dr. Venable: So you are using the checkpoint inhibitor with electro chemo. Or did you say gene immunotherapy.

Dr. Impellizeri: With the gene, the checkpoint inhibitor with the gene and electro transfer. So instead of just providing the immunotherapy as a standalone we’ve been doing, we’re now combining it with the checkpoint inhibitor, the PD one inhibitor. And I can tell you that it’s very much mimicking what’s being able to be offered on the human side. So exciting. We’re really hoping to show some data on that when we can, but I like the idea because it’s mimicking what’s currently the standard on the human side.

Dr. Impellizeri: So that always is something that clients want to hear.

Dr. Venable: That is really interesting. And I will definitely be looking forward to seeing that data, and also when we can get that more commercially available, the gene transfer.

Dr. Impellizeri: It's been frustrating because I want more people to have it, but you need to have the consistency of the same machine, the same people that know how to do it the exact same way. So it takes a little bit of training and commitment. But I think especially as we move towards the interest in these technologies, it’s inevitable. And I do think you’re going to start to see more and more people that are, hey, how can I become part of this and have.

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.