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Discussion Guide and Transcript

Season Two - Episode Five

Research Ethics Reimagined Season Two - Episode Five "The Intersecting Ethics of Canine and Human Cancer Research With Mark Mamula, PhD"

  • In this episode of PRIM&R's podcast, "Research Ethics Reimagined," we explore groundbreaking cancer vaccine research for dogs with potential implications for human cancer treatment. Our guest is Dr. Mark Mamula, Professor at the Yale School of Medicine and leading researcher in immunology and innovative vaccine development. Listen on Spotify | Listen on Apple| Listen on Amazon
Discussion Questions
  • 1.) Translational Research and Comparative Oncology
  • Dr. Mamula explains how his background in autoimmune disease research led to developing cancer immunotherapy, noting that attacking tumor tissue is similar to how the immune system attacks healthy tissue in autoimmune diseases. How might this cross-disciplinary approach to research lead to unexpected breakthroughs?
  • The research uses identical protein sequences (neoantigens) found in mice, dogs, and humans, allowing direct translation between species. What advantages does this comparative oncology approach offer for both veterinary and human medicine?
2.) Ethical Considerations in Veterinary Research
  • Dr. Mamula discusses how ethical decision-making differs between veterinary and human medicine, noting that pet owners make treatment decisions while human patients typically follow physician recommendations. How do these different decision-making frameworks affect research design and informed consent processes?
  • The research involves companion animals with naturally occurring cancers rather than laboratory animals with induced disease. What ethical considerations are unique to this type of research, and how might this approach influence public perception of animal research?
3.) Innovation and Regulatory Oversight
  • Dr. Mamula describes the extensive safety monitoring conducted through local IACUCs and USDA oversight. How do regulatory frameworks for veterinary therapeutics compare to those for human medicines, and what challenges might researchers face when working across both domains?
  • The research team had to collaborate with veterinary practices since Yale lacks a veterinary school, and Dr. Mamula founded a company to manage the therapeutic development. How should researchers navigate the complex relationships between academic research, industry partnerships, and regulatory compliance?

Key Terms

Neoantigen: A new protein that the immune system has never encountered before, which can trigger immune responses against tumor cells while avoiding immune tolerance to normal tissues. Comparative Oncology: A field that studies naturally occurring cancers in animals as models for understanding and treating human cancers, recognizing that many cancers are virtually identical between species.
IACUC (Institutional Animal Care and Use Committee): A committee that reviews and oversees research involving animals to ensure ethical treatment and regulatory compliance.
USDA (United States Department of Agriculture): The federal agency that regulates veterinary therapeutics and animal welfare in research, including companion animal clinical trials.
Additional Resources

Transcript


Ivy Tillman: Welcome to Research Ethics Reimagined, a podcast created by Public Responsibility in Medicine and Research, or PRIM&R. Here, we talk with scientists, researchers, bioethicists, and some of the leading minds exploring the new frontiers of science. Join us to examine research ethics in the 21st century and learn why it matters to you.
Catherine Batsford: I'm your host, Catherine Batsford.
Lisa Donnarumma: And I'm your co host, Lisa Donnarumma.
Catherine Batsford: In this episode, we are joined by Dr. Mark Mamula to discuss his team's development of a novel cancer vaccine for dogs, research that's showing incredible promise. Dr. Mamula is a professor at the Yale School of Medicine and a leading researcher in immunology and innovative vaccine development. His groundbreaking work on this novel cancer vaccine for dogs has garnered attention not only for its potential to revolutionize veterinary medicine, but also for its implications for human cancer treatment.
Thank you so much for joining us today.
Mark Mamula: Thank you for that kind introduction. Too kind, actually. It's great to be here.
Catherine Batsford: Can you start by sharing a bit about your background and how you became involved in this innovative cancer vaccine research? Mark Mamula: Yes, thank you. As you mentioned, we have initiated some studies in novel cancer therapies. And at the moment, at least, we've applied this to treating canine cancer, companion animals as it were. And I did get into this fairly honestly. I'm an immunologist by training. The history of my work here at the Yale University School of Medicine is in studying mechanisms of autoimmune diseases such as systemic lupus erythematosus, type one diabetes. There are a number of other autoimmune diseases that are relatively similar. Multiple sclerosis, for example. So, in studying, having studied those diseases for several decades, we've learned a lot about how our immune systems function and almost as importantly, how they dysfunction in creating these or triggering these autoimmune diseases. So, very, very simply put, these autoimmune diseases are immune responses towards your own tissues. In multiple sclerosis, for example, you have immune responses that attack your own nervous system that create the pathology of that disease. In Type One diabetes immune responses attack the pancreas, the cells that make insulin for example. Now, that is a direct correlation of how those immune responses happen. For us, for immunologists, I should say, attacking a tumor tissue, which is really a self-tissue is very similar to how your immune system attacks your central nervous system or your pancreas, for example. So, we wanted to learn or actually apply what we've learned about how our immune systems attack tissues, specifically how they attack tumor tissues and can we learn from both of those processes. So that's how we got into it. More emotionally for me is that I'm a dog lover. I have had a dog that did not survive cancer and this is now gosh, ten or twelve years ago. So, it's really drawing on my experience to apply these to treating canine companion animal cancers. Lisa Donnarumma: As a dog lover myself, Mark, I lost a dog two years ago to Hemangiosarcoma cancer. It was a very quick, and unfortunate, timely passing. I currently have a dog with a mast cell tumor. I'm finding more and more amongst my friends. I also compete in canine agility that many dogs, especially large breeds, are coming with this diagnosis of cancer. Hemangiosarcoma is probably the worst, the worst I've ever seen. The mast cell tumor, at least there's some hope for it, but you know it's such an epidemic. Mark Mamula: Yeah. Hemangiosarcoma is a very aggressive cancer, as both you and I know. My own dog passed away from Angiosarcoma, cardiac one and as you point out, these things progress and proceed very, very quickly in terms of weeks almost and survival is very limited in dogs with those cancers. But it’s interesting you mentioned that particular cancer; presently clinical trials are directed at treating Hemangiosarcoma’s as well as Osteosarcomas and what is called transitional cell carcinoma in dogs and that's bladder cancer. So, osteosarcoma is obviously a bone cancer. It's quite common in dogs, less common in humans, but nonetheless, how those diseases are initiated, progress, and metastasize are virtually identical between dogs and humans. We can discuss more about some of how that happens as well. But suffice it to say the tools that veterinarians have in treating dog cancers are much more limited compared to what we have in human cancers. So, my role and interest in studying dog cancers is not only as a translational model for understanding human cancers but by necessity and by interest is in expanding that toolbox that veterinary oncologists have in treating their own patient populations, treating dogs.
Catherine Batsford: So in the Yale News article, it describes that this incredible promise of the vaccine shows for treating the cancer in dogs. What makes this approach so novel compared to traditional cancer treatments, which you're just saying are fairly limited for dogs, but a vaccine is so exciting to think you can just prevent it from the onset.
Mark Mamula: Well, you bring up obviously a couple of very interesting points. It is described as a vaccine. We also describe it as an immunotherapy, which is maybe a little classier term for it. They, in honesty, use of the term vaccine that has several different implications, is true. It is connected to infectious disease for example, but in the context of cancer, we more often describe it as immunotherapy. It is an injection, of course, and it triggers immune responses, hopefully, that attack tumors. That's the nature of both our basic research studies as well as our clinical trials in defining how immune responses can attack these tumor tissues. The approach is, again, one that we studied in autoimmune diseases, and it's roughly described as a neoantigen. Neoantigen simply means it's a new antigen. It's a new protein that your immune system has never seen before. Give you thirty seconds of a class in... Lisa Donnarumma: Immunology? Please do. Mark Mamula: Immune systems have evolved to ignore our self-proteins. Your white blood cells bump into cells of your liver and your kidneys or your pancreas or your central immune system, central nervous system, I'm sorry, and tend to ignore what they see there. We're tolerant of most of our self-tissues. Now, that's not a perfect system. It evolved because we do have autoimmune diseases where those white blood cells bump into lots of tissues and start to attack them. Fortunately, those cases are relatively rare. Our immune systems evolved to protect us from pathogens, bacteria, and viruses primarily, and they see those as foreign. So, a neoantigen is something that is also foreign and can be in some cases, parts or portions of proteins on your own tissues. Those own tissues include tumors. So, this is an approach using a neoantigen, a tumor protein that your immune system has presumably not seen before. We and others have studied this both in autoimmune diseases and triggering autoimmune diseases, as well as in triggering immune responses to tumors. We're not alone in our own group. It's not unique to us and we did not invent the field of neoantigens, but we've exploited it. So that is part of, I mean, you ask what makes our approach novel. I'd like to think that we picked the right neoantigens from a family of tumor proteins and that were smarter than the other people in having defined these. That really was the intellectual work in developing these therapies. We pick on a family of tumor proteins known as EGFR and HER2. You may have heard of these proteins. They're fairly public in the domain of knowing these therapies. You see commercials, for example, for immunotherapies for a number of these proteins. There are drugs, there are monoclonal antibodies that are used in human cancer therapies. Herceptin is one of them. I'm not bumping into any particular product that binds HER2 proteins that are found on a fraction of human breast cancer, colon cancer, and a number of other cancers in human therapy. Erbitux is another monoclonal antibody that binds EGFR and, again, is found on a number of human and canine cancers, including hemangiosarcoma and osteosarcoma. So, the goal of our therapy is to provide an immunization and injection that triggers immune responses that have the biological activity of these drugs presently used in humans, Erbitux and Herceptin, for example. And indeed they do. We've demonstrated and published about those mechanisms.
Lisa Donnarumma: What would you say were some of the biggest challenges your team faced in developing the vaccine, both scientifically and ethically? Mark Mamula: Terrific questions. Scientifically, we had to get lucky. I'm not ashamed to say we failed in trying to find a number of these neoantigens. It was through the work of a number of people in our own lab, and in others, in picking parts of this protein family; actually, small regions within the proteins that exist on the surface of tumors to find them and to test them. First in mouse models of cancer to see if we could identify these so called neoantigens that trigger immune responses to tumors. We failed in a number of attempts, and we were successful in a number of attempts. We picked, of course, the successful ones to develop in uses in both veterinary oncology and potentially human oncology. You ask about the questions of ethics and moving forward with these therapies. I knew you were likely to ask that question. And I have it in front of me, the Webster's dictionary definition of ethical, the term ethical. As I read, it's pertaining to or dealing with morals or the principles of morality pertaining to right and wrong conduct. And as a second definition, being in accordance with the rules or standards for right conduct of practice, especially in the standards of a profession. Okay, so what is the standards of this profession? Meaning the veterinary professions or in human cancer care, that profession. Certainly, the definition of ethical is probably different in veterinary care and in human cancer care. How is that? We want to, of course, provide ethical therapy either in veterinary care or in human care. But again, those definitions I think do differ in a number of important ways. You're going to ask me what ways. I'm going to give you my opinion of that. For example, treating your dog and, Lisa, you can identify with this approach as well.
Treating your dog ethically is very different than treating a human with cancer. You, as the owner of your dog, have the decision-making process in treating your dog. That process is different. It largely can be dictated by things like cost, right? Or economics of treating your dog. If you don't have the resources to treat your dog with expensive care, you may choose not to treat your dog. That's your decision. It's not the decision of the veterinarian or the veterinary oncologist that is treating your dog. So, the mindset of course, for treating canine cancers, any companion animal in any way of course, whether it's cancer or any other condition, diabetes in a dog, lupus in a dog, heart disease in a dog is in fact, the decision of the owner. Choosing to do surgery, a decision again for the owner, is expensive, unless you have insurance for your pets, can be a costly option. Of course, treating human cancer is a very different decision-making process. You largely, hopefully, adhere to the recommendations of your human clinician. It's out of your control many times unless you choose not to be treated at all and of course, that's a whole ethical topic in and of itself. So while we attempt to navigate both human and veterinary ethical standards, they are obviously different. Catherine Batsford: So, we know there's debate about using animals in research. It takes on such a different tone in some ways when you're looking for the answers for your pets. So, what are your thoughts in general? How did your team ensure the welfare of the dogs involved while they were advancing this work? You said you used mice before you went to dogs, which is very similar to all animal research, even heading down to the human segment. Mark Mamula: So, I will rewind just a little bit. You asked about how we came to this line of investigation—this neoantigen line of investigation. Part of the intellectual input and process here was in using something in mice and in dogs that could be directly translatable—directly applicable—to human cancers. So, we chose a neoantigen to dive in, literally, to the details of this therapy. And it's published, so I'm not afraid to share any of the details. Of course, we picked an amino acid sequence—a string of amino acids in this tumor protein, EGFR and HER2—that was absolutely identical in sequence between mice, dogs, and humans. So, finding a successful neoantigen and therapeutic application in mice could likely be directly translatable, because it's an identical product—literally—between mouse, dogs, and humans. Okay. So, that lays the groundwork for how we thought about translating this care, hopefully with translation to humans, ultimately. In an intermediate sense, my interest is in dogs, of course. But you ask again about the ethical considerations. So, to me—and you guys can certainly correct me—to me, it is often a question of risk versus benefit, whether it's in mouse, dogs, or in humans. We all watch commercials for therapeutics in treating a number of human diseases. We watch them in commercials on TV, and we all know that the last part of any commercial are the side effects, right? Which can be death, for example, in the use of some therapies in a number of human diseases. So, the question in treating human diseases is always: do no harm. And it is, I think, in all of our minds to treat our own diseases. Whether it's heart disease or diabetes, for example, it's a risk versus benefit. What is the risk of taking a therapy versus the benefit, meaning, will I risk death, for example, if I don't take this therapy? Or will one of the benefits be curing or treating whatever syndrome or disease that I suffer from? And dogs, of course, cannot speak for themselves, but the owners can.
So, again, the ethics lie in the lap of—no pun intended—your dogs exist in the owner's lap, but also the question of ethical use lies in the lap of owners as well. Catherine Batsford: Well... Mark Mamula: I'm not trying to evade the question. No, I'm trying to point out the distinction, I think, between considering canine cancer care versus human. Catherine Batsford: I think that is clear. Mark Mamula: Having said that, though, we do carefully monitor the safety issues of our own therapy. First done in mice, of course, and we carefully looked at potential off-target effects, any pathologies that might be created by our therapy. And we were very, very careful. I'll tell you, there was nobody that lost more sleep in the first month or two of our clinical trials in dogs, which are still ongoing. We've now survived almost five years of trials in canine cancers without any immediate untoward off-target effects. No immediate hypersensitivity, which is a potentially common outcome of many drugs that are used not only for cancer care, but other care. For example, you—again, the disclaimer in seeing commercials on TV is—"don't use if you are allergic to X, Y, and Z that are in our therapy." Of course. Of course, no one would use that if you're—if you have some immediate allergy or hypersensitivity to—but again, we don't know if we do, most frequently. We don't know what the components of a particular therapy are. So, those are a bit superfluous questions because, as an end user—meaning you or me or the dog patient—we don't necessarily understand or know if there is hypersensitivity to any drugs we use until we experience them, of course. And your doctor says, "Oh, you're hypersensitive." Oh, great. We now know that.
Catherine Batsford: So, the research has powerful implications for veterinary medicine. And I think you've talked about, you know, that connection to people, how you started your study design, and the oversight for it. So, I guess my question is—I'm not sure, because I think you answered a lot of them—was there anything that shaped this differently? I think, no, you always had the mindset that this was heading toward something for humans. So, it was part of the process all along. Lisa, do you want to go to your question? Lisa Donnarumma: Sure. Mean, in research like this, how do you balance urgency for developing lifesaving treatments with the need for rigorous ethical review and patient or participant safety along the same lines? Catherine Batsford: Okay. ’Cause we all want to save our dogs, right? Mark Mamula: I'll tell you what, it'll sound like I'm digressing a bit, and I'm not trying to, and I'm not avoiding your question. I will certainly answer any of your questions. But you and I, Lisa, have both experienced, as dog owners, aggressive—an aggressive cancer that our dogs did not survive. And we know how quickly that arose. So, I think at least for you and me, having direct experience, our judgment or decision-making in deciding to accept therapy or not is based on real-life experience. I know that if I have a dog—another dog—with hemangiosarcoma, I will be quick to use any new tool in treating that cancer. There are similar cancers in humans, of course, that I think any of us would accept as a new therapy, investigational or not, in treating that cancer and in knowing the likely outcome of, for example, a canine cancer like hemangiosarcoma. So, the bar is very different for you and me, Lisa. Potentially, a dog owner who has never had or experienced a dog with hemangiosarcoma—in spite of what a veterinary oncologist will tell them about the disease, in spite of what anyone can read about this cancer in dogs—there is nothing like personal experience. So again, it's a benefit versus risk question to me. And everyone will decide that slightly differently. But I'll tell you, the best part of this study—and I get many emails from our patients, which now number upwards of 600 or 700 patients, canine patients—is that I get emails from generally elderly people, or disabled people, or both. They have a dog who is a service animal to them. And they say, "I need this dog literally to survive my day, to be a service animal to me." And they're trained in remarkable ways, of course, and I could go on and on in how many service animals are trained for specific purposes of their owners—be it seeing-eye dogs, or be it dogs that detect health issues in their owners, dogs that allow them to function on a normal daily basis.
They email me, and I could honestly well up when I hear these—when I read these emails. They say, "My dog now has cancer, and this is a dog that I need to survive. Can they have or think about our therapy?" And then the best part of this is getting an email from that same owner eight months, or a year, or two years later, after having had our therapy, saying, "My dog is doing terrific. Thank you." Catherine Batsford: That's incredible. Lisa Donnarumma: That's amazing. Mark Mamula: And I think you both read—or, and this is in, of course, the public domain—a service animal that we treated now several years ago. Yes. Hunter. Hunter was referred to me by—I could go on. You can stop me if I'm getting too verbose here. There was an undergraduate student here at Yale. He was the oldest undergraduate at this institution at the time, and could be in the history of Yale undergraduates. He was 52 years old. He was a retired service person, trained in the military—special forces, actually. And he did several tours of the Middle East. And he had a K-9 military dog that traveled with him. His military dog was killed in combat. He wrote a book about this experience, actually, but he later went on to fund a nonprofit organization to assist service animals of all kinds. And that can be military dogs. It can be police dogs. Could be trained firefighting dogs. So, we were referred to a dog in his organization that had cancer. This is a dog that was trained to find survivors—deceased individuals—in catastrophic building collapses, for example, which happen frequently, right? Tornadoes will level buildings, or hurricanes, and they're looking for survivors. This was a dog that was trained to climb through building collapses and try to find and seek survivors. Dog's name was Hunter. Hunter had osteosarcoma, had its front limb amputated, and had metastases to the lung, which is the primary cause of morbidity and mortality in this cancer in dogs and in humans, I might add. Hunter enrolled in our therapy and did quite well. In fact, is still alive now, I think three years after having gotten this cancer. And the owner—the trainer/owner—was happy to talk to us and to Yale about her experience. And Hunter continues to do well. We treat him annually with booster immunotherapies, as I described them. And so that was, yes, one terrific and visual outcome of what actually are a number of good outcomes in our therapy. We don't cure every cancer. That is never going to be the claim of what we do.
Cancers, of course, in dogs and in humans—therapies do not work the same in all cancers, even the same cancers in different humans or the same cancers in different dogs. So, the outcomes can vary between dogs and between humans. And we can talk about why that is. Simply put, it's because of features of the individual cancer. You and I can have the same cancer. I may have—I will have—different mutations, different genetics. We are of different age and different gender, and all of those characteristics change how an individual responds to a particular therapy. Again, both in dogs and in humans. Catherine Batsford: So, is this immunotherapy used in humans yet, or is it still with...?
Mark Mamula: This is not yet considered in human therapies. We've not initiated human clinical trials with this therapy. Other related neoantigen clinical trials are continuing to be investigated in human cancers. We hope that ours becomes one of them. My efforts and my bandwidth, quite literally, is in getting this out to canine cancers. And perhaps, when enough data—or more data—is obtained in treating canine cancers, the pathway to treating human cancers will be much easier. I will tell you that there is a field called comparative oncology that has continued to use canine cancers as—I was going to say models for treating human cancers—but they're not a model. They are a parallel disease that is virtually identical to human cancers. We talked about osteosarcoma—bone cancer—in dogs and humans. The genetics, the features of metastases, and the morbidity and risk of mortality are identical between dogs and humans. Such is the case. Dogs get melanoma, for example, that has many of the same mutations and features as human melanoma. So, this field of what we know—or what's defined as comparative oncology—is now being exploited for better treatment of human cancers. For example, treating human osteosarcoma often, if possible, starts with what's called limb-sparing surgery. So, instead of amputation of a limb with osteosarcoma—either in humans or in dogs—a surgical expertise that was pioneered in dogs, limb-sparing surgery, which is removing the tumor but putting braces into the affected limb to maintain the integrity of that limb without amputation, was first pioneered in dogs and is now widely used in human osteosarcoma. Lisa Donnarumma: We wanted to ask you about collaboration. That seems like a key part of the research. Are there any partnerships across the disciplines and possibly with pet owners influencing the direction and the success of the study?
Mark Mamula: That's also a terrific question. And we had to navigate that very carefully here at Yale because Yale does not have a school of veterinary medicine. So, how to solve that—which was another obstacle, a big obstacle actually—is we had to collaborate either with other academic institutions that have vet schools, or we had to, for lack of a better term, invade or penetrate private practice veterinarians. And we actually did both. We set up clinical trials with large veterinary oncology practices around the country and a consortium of veterinary practices called MedVet. I guess I must also reveal a potential conflict of interest, as it were. I did start a company—Therajan.com. In full disclosure, this is a company that will hopefully and ultimately manage this veterinary therapeutic. So, we had to find—and this is all USDA-regulated. The USDA regulates everything that's done in animals—not only companion animals or pets, but also in cows, horses, pigs, sheep, goats—everything. Food animals, any therapy, bird flu, chickens, for example—all regulated by the USDA. The FDA regulates some veterinary products but mostly regulates human therapies. But we have a USDA-approved exploratory study, as they call it, for the product that we are trying to better understand and develop. And ultimately, they will license Theragun to use this and to widely distribute that, hopefully. And we're hoping to get that in the coming months. The timing of how those—it's, as any government process, very time-consuming. There's a lot of bureaucracy, but they carefully regulate these things for very good reasons, of course. Catherine Batsford: How does an IACUC play into this—for the folks on our IACUC committees and interest in this? At what juncture is the IACUC involved? Mark Mamula: IACUC's involved both locally. The USDA is essentially our IACUC for clinical trials. But our local IACUC has reviewed all of our protocols for use in mice and actually use in dogs as well. But again, we don't have a vet school here, so the use in dogs doesn't necessarily pertain to what we do locally, but more outside the institution. Catherine Batsford: Were there any unexpected questions that popped up working with them, or was it smooth sailing? Mark Mamula: Oh gosh, all sorts of questions, as you might imagine—including the obvious things: dosing, toxicity. Did we do all of those things? And, simply put, yes, we've done all of those things, starting in mice. And in early studies in dogs that have received our therapy, we've looked at pathology of every tissue of recipients of our therapy from—gosh, literally every tissue—brain, heart, lung, liver, heart, skin, GI tract—for off-target, potential untoward effects. So yes, we had to dot I's and cross T's at every step. Important—yes. So, if any listeners of this broadcast have dogs, like Lisa or myself, that are suffering from, at the moment, osteosarcoma, hemangiosarcoma, or transitional cell carcinoma, there are a couple of sources—resources—that one can find clinical trial sites for our therapy. They are listed on the theragun.com site. They are also listed on another site—the Canine Cancer Alliance. You can Google that. They list all of our clinical trial sites. They are a nonprofit organization dedicated to curing canine cancers. And again, full disclosure: the Canine Cancer Alliance supports our clinical trials so that our patients receive our therapy at no cost. At least for our therapy—they may experience costs involved with treating their dogs with chemotherapies or office visits at the clinical trial sites—but our therapy is provided at no charge. Catherine Batsford: We'll make sure it's included in our study guide. Lisa, go ahead. Lisa Donnarumma: I was just going to ask about it, I'm sorry, that's my dog. Catherine Batsford: No, it's perfect. Lisa Donnarumma: They protect UPS in the neighborhood, not bombs, or people missing. This is their job. Mark Mamula: No, I think your dog is agreeing with my comments about treating dogs. Lisa Donnarumma: Right! For researchers hoping to push boundaries with their own work, what advice would you offer about maintaining strong ethical principles while pursuing their innovation? Mark Mamula: Again, a great question. My advice is to pay attention to your local institution, IACUC, and standards of care—not only in dogs; in fact, probably not dogs. I suspect most of your listeners are doing investigations either in humans or in other animal models—and to carefully consider and take the advice of those that they consult with, be it IACUC or other regulatory agencies. I personally take those regulations extremely seriously to reduce potential pain and suffering associated with doing new investigations. One will always experience unanticipated consequences of therapy. Our own therapy, for example—we did observe in early studies that a small fraction of our dogs will get inflammation at the site of where our therapy is injected. It is only about one in five dogs, about fifteen to twenty percent. It will be a little lump under the skin where the injection site occurs, but that nonetheless is one side effect. It fortunately is not painful to the dogs. And in fact, injections like this—or immunizations, as even humans experience—you know that sometimes there's some "oh" at the site of, say, a flu vaccine in your arm. There may be pain and/or mild fever for a couple of days after any human immunization. As an immunologist, I would like to say that is actually a good sign—that you feel a little pain or a little fever. What that means is that your immune cells, your white blood cells, are at the site of that injection, and they're starting to take in and digest and process that immunization. You will have a very good immune response, generally speaking, when that site reaction occurs. And such is the case, actually, in our dogs that get those minor reactions.
Catherine Batsford: It's good to know. What is next for this immunotherapy?
Mark Mamula: What is next? Well, ultimately—well, in the short term, I'll take the short and long term here—we are attempting to get licensing. It's called conditional licensing from the USDA. So, in the shorter term, we are seeking conditional licensing that will allow us wider distribution of our therapy. It will also potentially allow us to examine other tumors in dogs that have this family of proteins, EGFR and HER2. In dogs and in humans, that includes breast cancers, some breast cancers, colon cancers, some melanomas, non-small cell lung cancer. In dogs, it also includes anal sac carcinoma, soft tissue sarcomas, thyroid cancers, as well as some adenocarcinomas. So, there is a much larger laundry list of cancers that we may be able to treat in dogs—and, again, providing important translational data for potentially treating humans with those same cancers as well. The latter will be the much longer-term goals of our therapy: providing efficacy data for those other tumor types and providing seed data for studying those cancers in humans with our therapy. Catherine Batsford: When you went through that list, I don't know anyone who hasn't been affected by one of those—for dog or for human. Truly.
Mark Mamula: Glioblastomas as well—another important human and canine cancer as well. But you're right. Yeah, we've all had, you know, acquaintances—either canine acquaintances or humans—with those cancers. Lisa Donnarumma: Yeah. Well, thank you so much, Dr. Mamula, for joining us and sharing your insights on this incredible research journey. And thanks to our listeners for tuning in to Research Ethics Reimagined. Be sure to subscribe and join us next time as we continue exploring the evolving world of research ethics.
Mark Mamula: Thank you again. It's been a pleasure being here.
Catherine Batsford: Thank you. This is incredible. Was that Ben, or was that Jerry?
Lisa Donnarumma: That's Jerry. Yeah. Mark Mamula: Great dog names—Ben and Jerry. PRIM&R: Thank you for listening to Research Ethics Reimagined, a podcast created by PRIM&R and produced by Syntax in Motion. Please subscribe and share with your friends and colleagues. To learn how to become a member of Primer, please visit us at www.primer.org. Be sure to join us next month as we continue our conversation with scientists, researchers, bioethicists, and some of the leading minds exploring new frontiers of science.
Research Ethics Reimagined guests are esteemed members of our community who generously share their insights. Their views are their own and do not necessarily reflect those of PRIM&R or its staff.