Cancer Vaccines??? Dr. Chris Pirie, Co-Founder & COO of HDT Bio
Some of us live with the specter of cancer as a genetic inheritance, perhaps the famous mutations of BRCA 1 and BRCA 2. For others, it can simply be an undeniable family history. Others of us may only suspect past exposure to a myriad of toxins found in modern life. Regardless, what if your immune system could find and target those cancer cells and remove them? Doctor Chris Pirie is the cofounder and COO of HDT Bio.
Dr. Moira Gunn:Doctor Pirie, welcome to the program.
Dr. Chris Pirie:Thank you, Moira.
Dr. Moira Gunn:When we talk about medicines and cancer, we generally think of treating a cancer that exists. But you're talking about preventing people from getting cancer in the first place. How does that work? How is that possible?
Dr. Chris Pirie:Well, we're all familiar with sort of classical vaccines, whether we got them when we were kids or we got them for our kids or maybe even more recently in the pandemic, you got a vaccine. You know, all of these classical vaccines are focused on preventing infectious diseases like viruses or bacteria. But the principle is generally the same that you're showing your immune system a part of that, virus or bacteria and telling it what to look out for. Like, should you ever encounter that infectious disease? And when we think about trying to prevent cancer with vaccines, the principle is generally the same.
Dr. Chris Pirie:And in fact, in that vein of infectious disease vaccines, we actually have a tremendous example of how one can prevent cancer using these tools in the form of Gardasil, which was originally developed as a vaccine for human papillomavirus. And upon its approval was indicated principally for adolescent girls. But what we came to learn as we continue to adopt this vaccine was that we were actually able to prevent cervical cancers and other types of cancers that had long been associated with the HBV virus. And now the, use has been really expanded even to adolescent and adult, males as well. Because in some regions where the vaccine has been well adopted, we've seen almost a complete eradication of cervical cancers thanks to preventing a viral infection.
Dr. Moira Gunn:Well, it's sort of interesting to me. It's like you don't even have to know the link from how you get from the human papillomavirus to the cervical cancer. If in fact, you just don't have the presence of the virus, you're not gonna get the cancer.
Dr. Chris Pirie:Exactly right. And there are any number of other, sort of viral associated diseases that we're now thinking about trying to prevent by going after the virus first and preventing the viral infection by vaccination.
Dr. Moira Gunn:Now let me take a slightly different, angle here and that some women are born with the BRCA 1 and or BRCA 2 mutations, which can which make them more liable to breast or ovarian cancer. What would be the approach there?
Dr. Chris Pirie:Yeah. It's exactly right. So, you know, all of us are born with these sort of predispositions, whether it's for cancer or some other type of disease. And so when we think about preventative care, and indeed vaccines are one of the greatest examples of preventative care, then and we wanna apply that to cancer vaccines, then we can look at both your inherited mutations, like BRCA 1, BRCA 2, or your acquired mutations that you sort of pick up just by living and breathing or sometimes by environmental factors. And we can think about vaccinating against those types of mutations in order to prevent different types of diseases, including cancer.
Dr. Chris Pirie:And when, you know, you you think about those different types of mutations whether, inherited or acquired, there are many which are associated with a specific tissue type and or a specific cancer. And it's on those particular types of mutations that we wanna focus when we think about developing cancer vaccines.
Dr. Moira Gunn:Well, if I think about the mnra vaccines, which you mentioned with COVID, they were focused on the the DNA of that spike protein on the COVID. So would you be focused on the BRCA 1, BRCA 2 mutations as an example?
Dr. Chris Pirie:Yeah. As an example of a a cancer associated mutation is exactly what we wanna look at. However, we we'll tend to focus on those subset of mutations that are specific to the tissue or tumor that, you you know, you're sort of exhibiting or you're predisposed to. Now, the mRNA technology that, as you point out, arose during the pandemic, really gives us a unique toolkit for being able to do this. You know, there's there's 2 features of mRNA technology that, you know, lend themselves to cancer vaccines.
Dr. Chris Pirie:The first is the ability to get your body to express the mutant protein. Because a lot of these mutant proteins are very difficult to manufacture. But if we can do it in your own cells, then it's all that much easier. And then the second is the speed of response. We saw that speed during the pandemic when we had in a new virus we've never seen before and how quickly were we able to develop a new vaccine.
Dr. Chris Pirie:The same is applicable when you think about vaccinating against tumor specific antigens that are specific to your own, like a personalized cancer vaccine. And in that setting, it's really important to be able to sequence your cancer following a biopsy, for example, and then to encode those mutant proteins into an RNA and then vaccinate it with you. And and then all of a sudden, your immune system is aware of your specific cancer wherever it is in your body. And so that that when you combine those two things, it really opens up our ability to develop these new cancer vaccines.
Dr. Moira Gunn:So in that sense, there are many tools now to address how we might develop a cancer and to get in there early.
Dr. Chris Pirie:Yeah. Absolutely. So more and more, we want to think about developing cancer vaccines that are truly preventative. So, you know, Gardasil again being a prime example. But now with these new tools, we can think about developing preventative cancer vaccines that adopt not only infectious disease proteins, but start to look at those inherited or predisposition type of mutations that, are acquired or, say, lead you down the path towards a cancer before it actually ever becomes cancer.
Dr. Moira Gunn:Let's get down to exactly what HDT Bio is doing. I know you're working on prostate cancer, pancreatic cancer, and breast cancer. They're 3 separate programs. What are they doing? What's different between them?
Dr. Moira Gunn:Where are they the same? Tell us about that.
Dr. Chris Pirie:Yeah. These programs were really born out of the success of HDT's early vaccine work, again, in infectious diseases. And what we learned from those clinical trials was that our vaccine platform had some really unique features in both safety and cellular immunity, which is an important feature for developing effective cancer vaccines. And so we established some collaborations with folks at the National Cancer Institute, at Johns Hopkins University, and at the University of Washington Cancer Vaccine Institute. And across those, we've been able to combine our vaccine platform with some very well established cancer mutations that are found as you point out in either prostate, breast, or pancreatic cancers.
Dr. Chris Pirie:Now those candidate vaccines are still in preclinical development. But what we're seeing in terms of cellular immune responses in those preclinical studies are really compelling based on historical publications of correlations between those cellular immune responses and improvements in overall survival for cancer patients.
Dr. Moira Gunn:It's too much to ask. Okay. Great. We're going to give you a vaccine and check the next 20 years and see if you develop that. This is like not we're looking for now.
Dr. Moira Gunn:So, you're taking people already with the cancers of pancreatic, prostate, and, breast. And you're seeing, let's give you these and see if we can detect an immune response. Did I get that right?
Dr. Chris Pirie:Well, we want folks ideally who have, yes, been diagnosed with those respective cancers, but have undergone, you know, sort of standard of care treatments and have been fortunate enough to find themselves in remission or cancer free. And then we can come in and give them our vaccine and then monitor their progression or so called disease free survival. And, you know, it's it's a 2 common, concern for cancer patients that they're going to relapse, that their cancer is gonna come back, whether it's in the same tissue that they had the cancer originally or if it metastasizes to some other tissue. And and indeed depending on the cancer type, you can have to wait many, many years to follow these patients and wait to see whether or not their cancer comes back and whether or not your cancer vaccine made any difference in the rate at which or the frequency at which it's coming back. So one of the things we'll do in early clinical trials is take blood samples and measure whether or not your immune system has mounted a cellular response against the very specific mutations that we've given to it in our vaccine.
Dr. Chris Pirie:And depending on the magnitude of those cellular responses, we can have a a very strong confidence as to whether or not those that immunity is now going to help prevent the cancer from coming back.
Dr. Moira Gunn:This is just so fascinating in so many ways because cancer seems huge. Obviously. It is huge. I'm not saying it's not. And and for so many years, we we thought there was breast cancer and then prostate cancer.
Dr. Moira Gunn:These were all different cancers. Then we understood, oh, it's all one cancer. Just happens to be where it is in the body. But I I feel like we're getting our arms wrapped around cancer and we're sort of backtracking and say, what causes it? And and now we're finally at that place where we could have a vaccine or or set of vaccines that could prevent it in the first place.
Dr. Chris Pirie:Yeah. I I think that's exactly right. You know, we had historically our clinical diagnosis in cancer so attached to the tissue in which it was arising that as we learn more and more about the underlying drivers for cancers, as you rightly point out, they there are more commonalities than differences across some of these cancer types. And what that's empowering us to do, especially in the vaccine space, is to identify some of those commonalities and then to develop cancer vaccines that are, you know, perhaps cancer type specific, but not cancer type specific in the way that it's, oh, just breast cancer. It's really all cancers that carry that type of mutation.
Dr. Chris Pirie:And this is true of going back all the way to our example of Gardasil, where indeed the earliest demonstrations of cancer prevention were in a cervical. But now we are now also understand that this vaccination can help prevent head and neck cancers, for example. And so this awareness that we've been able to cultivate really has empowered a broader ability to develop cancer vaccine candidates that prevent broad, cancer types.
Dr. Moira Gunn:So the more we understand about cancer, the better we're gonna get.
Dr. Chris Pirie:Exactly.
Dr. Moira Gunn:Okay. Now you're testing a lot of people. You're working with them. They've had various kinds of cancers. You're seeing are we generating an immune response?
Dr. Moira Gunn:Hopefully, we're seeing better results in terms of relapse, if that's, you know, if that can be avoided or at least put out, you know, extended further. When are you gonna know what? How do you how do you decide that? How, you know, how do you move forward with this?
Dr. Chris Pirie:Well, as I say, you know, we're gonna measure the cellular immune responses early on. We do want to follow these patients and monitor the their cancer or or their rates of, relapse. But ultimately, these products will have to move through a traditional drug development pathway. So phase 1 clinical trial, phase 2 clinical trial, and so on. But ultimately, the goal is to bring these to market initially in patients who are, as I say, already diagnosed with cancer and find themselves in remission.
Dr. Chris Pirie:But what we wanna do is developmentally move our way upstream in the development of cancer. Because, you know, we really wanna be able to prevent you from ever getting cancer in the first place. The challenge there is that it often takes different types of mutations at the earliest stages of cancer versus the later. And so it will take fundamentally different vaccine candidates to operate in that truly preventative mode than it will for, you know, sort of prevention of relapse or metastases.
Dr. Moira Gunn:So an early cancer or precancerous condition might have a different mutation profile than full blown cancer.
Dr. Chris Pirie:Precisely.
Dr. Moira Gunn:And that's where it becomes a vaccine. So there's the early stuff, and that's what you gotta figure out too.
Dr. Chris Pirie:Yeah. I mean, this remains a challenge, to understand what are the set of mutations precancerously versus during the progression of the cancer, and when can we intervene with a vaccine to either help treat or prevent those cancers. And the expanding ability or availability of gene sequencing information across our entire property. You think about, like, 23andme. If you've ever done 23andme, you get this great profile of, you know, what are all the different type of predispositions you have.
Dr. Chris Pirie:High blood pressure, diabetes, cancer, what you name it. Right? Blonde hair, brown hair. Right? All these different things that you can learn from your genetic information.
Dr. Chris Pirie:As we are able to watch more and more people and gather their genetic information as they grow older, which of course, you know, cancer generally a disease of aging, then we can see in, you know, specific spots of your genes where these mutations arise and then where ultimately you develop cancers. And it's by that sort of broader awareness that we're gonna ever can you continue to improve upon diagnosing which mutations need to be vaccinated against to ultimately prevent those cancers?
Dr. Moira Gunn:You have a lot of work to do, doctor Perry.
Dr. Chris Pirie:I think we all do. It it you know, it's we're we're all hard at work trying to improve, these vaccines and all of the different diseases that we can prevent using them.
Dr. Moira Gunn:Well, doctor Pirie, thank you so much for coming on, and I hope you come back, keep us updated.
Dr. Chris Pirie:It's been an absolute pleasure. I'd be happy to.
Dr. Moira Gunn:Doctor Chris Pirie is the cofounder and COO of HDTBIO. More information is available on the web@hdt.bio. That's hgt.bio.
