When we consider how a vaccine works, we typically think about vaccines that prevent infectious disease like flu or measles. But another type, known as therapeutic vaccines, may be able to treat diseases even after they’ve taken hold in the body – including cancer and viral infections. Similar to preventative vaccines, these therapeutic cancer vaccines work by promoting an immune response. Cancer vaccines are an emerging approach that have the potential to train the immune system to better seek out and destroy cancer cells. Co-host Danielle Mandikian sits down with Lélia Delamarre, Director and Distinguished Scientist, Cancer Immunology, and Ina Rhee, Executive Group Medical Director, Oncology Early Clinical Development, to discuss the fascinating science behind cancer vaccines as well as current challenges and opportunities.
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Transcript of Two Scientists Walk Into A Bar: “Learning from Vaccines: Training our Immune System to Fight Cancer” with Lélia Delamarre and Ina Rhee
Maria: I’m Maria Wilson.
Danielle: And I’m Danielle Mandikian.
Maria: And we are scientists. We. Love. Science.
Danielle: Yeah, we do. So, when we aren’t doing it, the next best thing is to talk about science! What’s really awesome is we’re surrounded by some of the most brilliant minds in research!
Maria: So there’s always someone interesting to talk to. But there’s never much time to just chat at work. That’s why we are so excited to be hosting this podcast. We are going to step away from the labs today to talk to other scientists about the cool stuff they are thinking about, working on and imagining…
Danielle: … as well as how some of these discoveries just might lead to new medicines. So, grab your favorite drink, get ready to unlock your science brain and join us for Two Scientists Walk into a Bar…
Maria: The show for scientists, science geeks and the people who love them!
Danielle: Hi, everyone. Welcome to the show. Today, we're going to get the opportunity to talk about cancer vaccines. And I think this is a wonderful time to talk about it because, quite frankly, vaccines are on everyone's minds. What's really interesting is that every time we think about vaccines, we're always thinking about viruses. But what's really cool is that for a while, in the true fashion of science, we've been trying to take something that's been successful in one area and apply it to everything. In this case, instead of just trying to prevent disease with viruses, we're also looking at using vaccines to treat cancer. This has been around for a while, but unfortunately we've never quite been able to get there. But what's great is that all of these recent advances that we've experienced with sequencing, dealing with large data sets, has really brought a new life into the field. So today, we're fortunate enough to have Lélia Delamarre, who's an immunologist, who can really kind of bring the perspective of cancer vaccine development, as well as Ina Rhee, who's an oncologist, who can really kind of give a different perspective on how this field is trying to approach differences in patient populations and how is this going to happen effectively in the clinic. And hopefully the junction between both of these perspectives is going to be what we need to finally bring this therapy to patients.
Hey! Welcome to the bar.
Lélia: Thank you. We're delighted to be here.
Ina: It's great to be here.
Danielle: All right. So, getting into it, one of the things that I think usually comes to people's minds who aren't as familiar with your work is, you know, taking a step back and saying, "Whoa, whoa, whoa. Cancer vaccine?" Normally when people think about vaccinations, they tend to think about, you know, viruses or bacteria. So, how is this really different from those kinds of traditional formats of vaccines that people think about?
Lélia: So, I think the major difference is – when we are thinking about vaccines for infectious disease, we are thinking about preventing the disease. And so, the goal of these vaccines is really to make antibodies to block the virus or the pathogens to enter and infect cells. In the case of cancer vaccines, it's not so much to prevent the disease, because the disease is already there. It's more about preventing the tumors to continue growing, and hopefully kill these tumor cells using the immune system. And so, in this context, it's not so much an antibody response that is needed, but rather we are trying to promote another type of immune response, which is T cells that can recognize specifically tumor cells and kill these tumor cells. So, that's what we are trying to do.
Ina: One thing that's really interesting is it is a spectrum of things that vaccines can do. So, you're right. We always think about prevention of infectious disease, and actually we can prevent infectious disease that causes cancer. So, everyone has heard about HPV or hepatitis B. And then, actually, the neat thing about cancer immunotherapy is you're asking your body to do more of what it's been doing all along to prevent cancer. So, we don't think about that, but T cells are presumably keeping cancer in check all the time, and recognizing runaway cells, and getting rid of them. So, we're trying to get vaccines to now address tumors that have somehow escaped that, but we're still tapping into fundamentally the same machinery: the immune system that can see a whole range of foreign cells or foreign elements.
Danielle: That's really interesting. What are some of the thoughts behind being able to get that nice differentiation between, like, the novel changes that pop up in the cancer cell versus having a vaccine that would accidentally recognize the cell that it originated from?
Ina: You know, I trained as a medical oncologist, and one of the challenges for all of our therapies is they don't just kill cancer cells; they kill normal cells. And just like we think about antibiotics, which work really well against bacteria – and the reason they work so well is they're attacking something in the bacteria that don't exist in human cells, a liability that is only a liability for the bacteria. That's the silver bullet we would like to have for cancer therapeutics. Is there a target we can drug that's unique to the cancer cell? And that's proven to be really difficult. It's the same issue with vaccines. If we had a marker or an antigen that the vaccine could train the immune system on that's truly unique to the cancer cell, we in principle would have a lot more success. And I think we know that cancer cells, if you look at their DNA, that they're different, but it's very hard to drug that difference. And it's not only vaccines. This is what makes cancer so hard to treat.
Lélia: Maybe I can add something to this, Ina. So, when we are thinking about vaccines, originally, the first clinical trials were really focusing on proteins, which are overexpressed by tumor cells. But they could also be expressed by normal cells. And, you know, it was just very difficult to generate a good T cell response. So, one thing we have to overcome with vaccines is tolerance. The immune system is tolerant against all the host proteins, and that is expected otherwise we would still have autoimmunity. So, there is really a high barrier of tolerance.
And so, a lot of the vaccines, the first vaccines were targeting normal proteins, proteins that could be potentially found in normal cells. And they were not generating very good T cell responses. And what happened in the early 2000s with the next-generation sequencing technologies, we have been able to sequence a large number of cancer cells. And we realized these cancer cells are accumulating – hundreds, sometimes even thousands – of mutations. And these mutations may potentially differentiate the tumor cells from the normal cells. And I think, for me, the big "aha" moment was when we realized, as a field, that the checkpoint inhibitors that are working so well at controlling tumors in patients, we saw efficacy with these checkpoint inhibitors in a population where the tumors had a very high number of mutations. And that was really where everybody made the link: There is a high number of mutations in some tumors, like melanoma, or non-small cell lung cancers. And these tumor types are actually responding to checkpoint immunotherapy. And so, based on these data, there was a lot of effort from the field to try to understand if these mutations that we find in cancer can actually be immunogenic, can actually elicit T cell responses that can kill tumor cells and control tumor growth.
Wellington: Hey Danielle!
Danielle: Hey, Wellington.
Stephanie: Hi, Danielle.
Danielle: Hi, Stephanie.
Wellington: Okay, so first question, what is a checkpoint inhibitor?
Danielle: So in the context she's using it, she's talking about something regulating whether or not a T cell is going to target another cell, in this case, a cancer cell. So checkpoint inhibition is saying, hey, remove those brakes.
Danielle: So, I know this is something that Stephanie and Wellington are definitely going to ask. If the tumor is already present, why do we call it a vaccine and not a therapy?
Lélia: So, for me, a vaccine is aimed at priming an immune response, or promoting this immune response. And you can prime an immune response against cancer cells. So yeah, for me, it's a vaccine from this point of view.
Ina: You know what's really funny? We've had that discussion a lot as we've thought about developing these, and one perspective has been: Look, if you call it a vaccine, people are going to be confused. You're not preventing anything. The person already has cancer; why are you calling it a vaccine? And so, I think we have thought about whether we need to characterize or label these differently. But now that everybody has COVID on their brain all the time and they have a deep understanding of vaccines, it's almost easier for us to explain to people now: Actually, this is a vaccine. It's training your immune system to see something foreign.
Danielle: You know, this idea of training the immune system is really interesting. I don't even know how we got there. What was the first vaccine?
Lélia: The first vaccine that was created was developed by a physician, a British physician, Jenner, and it was against smallpox. Smallpox was absolutely devastating in the 1800s. And so, what he noticed was that farm girls had beautiful skin. They never got smallpox. And it's because they actually got cowpox. And so, when they were milking the cows, they got cowpox. And this protected them from smallpox. So, he took the pus from their blisters, this live cowpox, and scratched the skin of people so that they would develop an immune response against cowpox. And this immune response would also protect them against smallpox. And that was the first vaccine that was developed.
Danielle: Okay. One thing that always cracks me up is scientists are always naming stuff after something, and there's always a backstory. So where do we actually get the word vaccine from?
Ina: The word "vaccine," as I understand it, is linked to the word "vaccinia," so the virus that causes cowpox I think is a vaccinia virus. And that is linked to a root word for cow, "vacca." So, I think embedded in what we call "vaccines" I think is this story about cowpox and the milkmaids.
Danielle: When I think about milkmaids, I think about like my grandpa who grew up on a farm milking cows, so it's kind of funny to think someone in that same position kind of started off this whole revolution, you know?
All right. Digression over. Let's get back to the science. So one of the things that always, oh how do I say this? So one of the things that always kind of blows my mind is just thinking within a single tumor, there's so many different mutations. So what would this look like as you're trying to dive into this across an entire different, you know, population of patients?
Ina: It's a really interesting question. So, we know that mutations are the basis of all cancers. We like to say that cancer is a genetic disease, and it is the accumulation of mutations that, in some ways, defines cancer. It turns out that pediatric tumors are often very genetically simple. They are characterized by a relatively few number of mutations. And actually, that's why they can arise in children who haven't even been alive for that many cell divisions. In contrast, there are tumor types, like melanoma, or lung cancer. Those tumors can have hundreds and thousands of mutations accumulate. So, there is a lot of diversity. And we actually see that translate into differential response to immunotherapy. As Lélia mentioned, some of the early promising results for immunotherapy were in very high-mutation burden tumors. And that connection between mutation burden and response to immunotherapy was an insight that was really important for moving this field forward.
Danielle: So, one thing that kind of I'm curious about is, you know, given that context – let's take like the pediatric tumors, for example. One thing that's sometimes kind of confusing, to me, is like at what point do you think about generating a vaccine that is more broad versus personalized, like, if it's more genetically simple, is there the opportunity to try to take, like, observed mutations that you see that are more simplified and translate that into a vaccine versus, like, having something that I imagine is more complex because there's way more mutations involved in it?
Ina: So, you're right. I think one way to think about a therapy is designing the therapy that will treat all patients of that class. For a pediatric tumor, many patients will have tumors that are defined by the same mutation. And so, in principle, we should be able to design a single vaccine that would treat many or most of those patients. The problem is that we would need to understand whether that single mutation actually is good at eliciting an immune response. And sometimes it turns out that, for whatever reason, the immune system doesn't see that single mutation particularly well. So, if you fast-forward to different tumor types that have many, many, many more mutations, I think there is evidence that many of the mutations that are best-recognized by the immune system are not the ones that happen in every single patient. They may be mutations that are incidental; they're not the ones driving the tumor. They're what we call passenger mutations. Those are often different from individual to individual to individual. And that's where you might need a personalized approach if it turns out that the very best mutations from an immune system point of view are not the ones that occur in all of the patients. So, I don't think we know this yet, but it may be that some of the more genetically simple tumors, like pediatric tumors, may not be the most susceptible to a vaccination approach. I don't think we have an answer to that.
Danielle: So, Lélia, I saw you shaking your head when Ina was talking about these different mutations. From the discovery approach, given that there are all these different mutations, what is it that you actually target for cancer vaccines?
Lélia: So, the immune system has developed a very simple method in order to be able to detect any change on normal cells. So, the role of the immune system is to be able to identify cells that are abnormal – either because they have been infected, or because they are transformed and are becoming tumor cells. And so, the immune system should absolutely control this. So, the cells, all are displaying their content at their surface, in the form of small peptides that are presented on MHC class I molecules to the T cells. And so, the T cells are surveying all these cells. And as soon as they recognize something – a peptide that is abnormal presented at the surface of a cell, then as a result they kill the cell. The peptides that are presented can be peptides that are derived from pathogens, if the cell is infected by pathogens, or could be a mutated peptide that is derived from a mutated cell protein.
Danielle: What you're saying is that all cells have a natural process where they're able to present examples of what proteins they have going on internally; and so, it's already a natural process that immune cells are constantly checking all cells to make sure everything is okay. They're constantly looking for that one presentation where it doesn't meet the library of what the body thinks is okay. Right? Or it doesn't meet up to standards. And so, once that abnormal peptide is presented, then what happens?
Lélia: Well, then once this abnormal peptide is presented, the T cells get activated and, as a result, kill the presenting cells.
Danielle: That's really interesting. So how is it that cancer vaccines actually tap into that mechanism?
Lélia: So, what we have to understand is if the mutation is actually presented by this MHC class I molecule at the surface of the tumor cell – and there are some very specific determinants that allow the peptide to be presented on MHC class I. And so, what the bioinformaticians are doing is they are collecting data from what we call the MHC class I ligandome. And trying to identify these determinants. And so, we have been also using intelligence artificial – artificial intelligence, sorry, the French person speaking here – to also better understand the rules of peptide presentation.
Danielle: So, that's getting a lot to what you had mentioned, that this also kind of helps bridge that gap to make sure that whatever it is that you're trying to use as a strategy is more likely to be immunogenic because it's able to be presented. Is that –
Ina: Yes. And as I'm thinking, I'm realizing – it's important to realize there is a paradox that we're trying to outrun here. So, cancers are defined by mutations. If the mutations lead to peptides that are too easily recognized by the immune system, the cancer will get eradicated by the immune system early on. It will not become a cancer. So, in some ways, we're up against cancers that may not be showing the most immunogenic of targets, or for whatever reason have already eluded the immune system.
Wellington: Danielle, Acronym Alert! MHC class I. What's that stand for?
Danielle: I like a challenge: That would be, Major Histocompatibility Complex.
Stephanie: Okay. But that doesn't actually help us understand what that is. Why is Lélia talking about an MHC class I molecule?
Danielle: Agreed. Acronyms are useless. Basically, this is a group of proteins that sit on the surface of cells. And what it does is it just kind of presents to all of the surrounding immune system what's going on inside of it. It gives kind of like a library of the proteins that are in the cell. And so, in the case of how this is interacting with the immune system, it's not until those peptides are presented that a surveying immune cell can decide whether or not there's something that's supposed to be there or not supposed to be there. I think there's actually two parts that are really important. The first is that, that set of proteins is kind of like this checks and balances system that we have that ensures that every cell that's in the body is in compliance as far as the immune system is concerned. And so what they do is they physically present these peptides which are like these little signature pieces of everything that's going on in the cell and the surveying immune cells will then scan it and be like, you're good, you're good. Or wait, here's the red flag that we need to go after.
Ina: So, I think one thing that's interesting to reflect on is that even though we're trying to use the immune system to attack cancer, in some ways the cancer we see has already evaded the immune system – otherwise it would not have been established as cancer. And so, we have to think about why did the immune system fail the first time or the second time, and how can we redirect or enhance the immune system to get it right? So, one part that we're very interested in is this whole issue of the target. Is the immune system trained on the right target? And we know that from the very beginning tumors are defined by mutations, but maybe those early mutations, or the ones that we consider driver mutations – the ones that actually cause the tumor cell to have runaway growth – maybe those aren't the most immunogenic. Meaning, maybe those aren't the ones that are best recognized by the immune system. And so, that's one aspect that I think the field has really gotten more sophisticated about, is tapping into the whole spectrum of mutations that distinguish cancer and normal – and finding mutations that perhaps do lead to much more immunogenic targets that we just didn't recognize before maybe because we didn't have the kind of sequencing technology we have now. In order to make vaccines work, though, there are probably other problems we have to solve, too. Maybe the T cells that encounter the antigen just aren't in the right environment. You know, we know that tumors have a lot of cytokines and other factors that are keeping the immune system suppressed, so there are other challenges – like the location, maybe, the physical location where the antigen is being shown to this T cell. And then, there's this issue of the cancer progression and when it goes from being a single clone that's gone awry, to being this really complicated and branched heterogeneous organism, almost. And maybe that's too late for the immune system. Maybe we need to back up earlier in cancer progression and spread to really be effective. So, I think those are all things that are really top-of-mind for us as we try to develop a vaccine approach.
Lélia: Yeah. And I also think that, you know, we have made a lot of progress in vaccine development. So, the vaccine field has been extremely successful at generating vaccines against infectious disease. You know, we have eradicated smallpox. We are controlling polio. And the latest success is COVID. We are not controlling fully COVID, but you know, less people are certainly dying from it. And so, you can see that we can relatively easily generate excellent immune response, which are antibody-based responses against infectious disease. It has been much more difficult to generate T cell response, CD8 T cell responses against cancer cells. And as we have discussed earlier, the difficulty was to identify the target, so we think we have solved at least this issue by identifying these tumor mutations. Now, the next issue is how do we design a vaccine that is potent at eliciting CD8 T cell responses? And that is much more difficult. We have now novel technologies that are based on a better understanding of how the immune system works, and these new modalities are much more potent at eliciting CD8 T cell responses than the previous vaccine platforms that were used even 10 or 15 years ago. And then, to add to this, we have also the checkpoint inhibitors and also modulators of the immune response that will help further promote the T cell response that is generated by the vaccine.
Danielle: I'm often thinking about the heterogeneity of tumors for a number of different reasons. And so, one thing that comes up in the solid tumor space is that, unfortunately, all tumors are different, right? And there are some sets of solid tumors where you have good immune cell infiltration, and other types of tumors where you don't have good immune cell infiltration. And so, from a vaccination standpoint, how do you approach – I mean, does having a tumor type that is less inflamed than another, you know, affect the likelihood of success for a vaccine approach?
Ina: I think that's a great question. I think, thinking about patients with different tumor types, as you've mentioned, yes, I think when we see a tumor type that already has T cells in it, that at least tells us that there's not a barrier to entry, per se. We know that if we can generate the T cells, it seems that they can get there. And so, what are the tumor types – or who are the patients who more often have infiltrated tumors? It may be those patients with melanoma or lung cancer, the patients who have many, many mutations and generate lots of T cell responses against their tumors. It's often in those same patients that we find infiltrated tumors. And so, from a drug development perspective and from a clinical perspective, those are often the first patient populations where we want to try these newer immunotherapies because we think there may be fewer barriers to therapeutic success. So, you're right. Tumor heterogeneity is a huge challenge for all of cancer therapy. One thing that's nice about this approach of using mutations as the target – of a cancer therapy like vaccines – is that there are many to choose from. And what we hope is that by targeting many mutations or many targets for a given cancer that we can address heterogeneity. Because even if a patient's tumor is actually comprised of three, or seven, or 10 different populations, and they may not share a hundred percent identity between them, if we choose multiple targets, it increases our chance that we can address each of those subpopulations within the tumor. And so, by using a tumor's mutations as a source of targets, we really do have the opportunity to select many targets to go after. That being said, the challenge there is then we really do have to tailor the therapy to the individual tumor's mutation repertoire, because we know from the sequencing work that's been done that it's relatively rare that one patient's tumor will have many mutations in common with another patient's tumor. So, that is the power of the individualized approach, is to be able to go deep into that well of mutations and hopefully combat heterogeneity.
Lélia: So, when we vaccinate, we want to generate a very high number of T cells against multiple targets, so that there are enough T cells to control and kill tumor cells. I think, you know, it's really a battle and a race between the tumor cells that are dividing and growing, and the T cells that are killing these tumor cells. And if there are not enough T cells to kill all the tumor cells, the immune system is going to lose. And that’s one of the reasons we are thinking also of starting, developing vaccines in earlier-stage disease, when there are less tumor cells, and the immune system may have an edge there. Alternatively, what we're also thinking – and at this point it's more wishful thinking than really something that is happening – but there is a belief that when the T cells are killing the tumor cells, these tumor cells are then releasing their contents, and they can be taken up by professional antigen-presenting cells that are then priming novel T cell responses against mutations that have not been the target of the vaccination. And so, this way, by killing tumor cells, we could expand the breadth of this immune response and generate these new T cell responses that could further control the tumors.
Danielle: So it's a lot like machine learning, but for your immune system.
Stephanie: Danielle, I wanted to talk more about tumor heterogeneity. It's a term that everyone throws around, but like, what are we actually talking about? Are we talking about the differences within an actual tumor or are we talking about the differences between different patients?
Danielle: Unfortunately, it's actually both. You know, what's so difficult in the oncology space is that, you know, when you're trying to treat a mass like a tumor mass, it's not all the same cell. There's all these different, like, you know, mutations that are going to arise. It's kind of like these masses of cells are totally unstable and there's changes that are just popping off left and right. And so within the single tumor, even though you might have it derived from one cell that's gone rogue, it's gone rogue because all breaks and monitoring systems for quality control are off. So not only does it mean the cell is going to be dividing, it also means that there's different genes that are going to be turned on, turned off. And you can't control for what that's going to look like. And it makes it really hard from a therapeutic standpoint, because you may have cells that express some kind of like signal that identified as being unique. And unfortunately, that same kind of signal can be lost within the same tumor site. And you imagine this is within one person's tumor. Now start thinking about that across a population, it's very difficult to try to get a handle on. And that's why this is such a cool topic of research, is because this is a very unique strategy compared to other like, you know, single agent approaches, because then you can take into account all of that heterogeneity both within a tumor and across patients.
Wellington: And was I understanding that two tumors within somebody's body could be different, too?
Danielle: It can be, especially if there's been metastasis where you have part of the tumor is broken off, gone to different – and, you know, really what's happened is it's gone to a different microenvironment. It goes to a different tissue, there's different signaling cues, and all of that kind of plays into what is going to be naturally selected within that tumor. It's wild.
Danielle: How has, you know, COVID impacted your work in the vaccine field?
Ina: I think just at a superficial level, people are just really interested in vaccines. And so, I do feel just we get more everyday questions that are about vaccines, about COVID, about what we think of a certain COVID vaccine. But it's been striking just feeling the energy around interest in how your immune system works, and interest in where the field of immunotherapeutics is going. So, I just feel energized by that because I think there's a lot of just thought energy being directed at what the power of the immune system is. And it's been exciting I think for all of us, who are working on cancer vaccines, to kind of dive into the COVID literature also to understand what can we take away from this, from the therapeutic success? What learnings might apply to the way we're trying to push cancer vaccination?
Lélia: Yeah, I totally agree. I think to add to what Ina said, what I find very exciting is that there are these new vaccine platforms that are now being tested, evaluated against COVID. And we learn a lot about the promises of these vaccines. So, you have RNA-based vaccines, DNA-based vaccines, or even viral-based vaccines that are being evaluated. We can now compare them by looking at the literature and better understand what the potential of these vaccines are – not only for infectious disease, but potentially also for cancer. Because not only these vaccines are eliciting strong antibody responses, but we can also observe that they induce CD8 T cell responses. And these T cell responses are what we want for a cancer vaccine.
Danielle: What inspired you to get into studying cancer vaccines?
Ina: So, for me it's very roundabout. I trained as a medical oncologist, but I also trained in science as a cancer geneticist. And in my drug development work, I can say it feels like coming back full circle, because when I was in graduate school, I was very focused on the mutations that lead to cancer through the multistep acquisition of different oncogenes and tumor suppressors. And now, I think to see the way that the genetics of cancer is being targeted by the immune system, I do feel very much that the field has moved to a place that I couldn't have anticipated. And it's super interesting and really satisfying.
Lélia: So, for me, I've always been interested by how the immune system is primed and how we can generate T cell responses against a given antigen. And I was particularly interested in dendritic cells, which have these unique features that make them excellent at priming T cells. And so, from there, you know, it's just easy to think about how we can manipulate the antigen, or we can rationally design a vaccine based on our understanding of how the immune system works, and how we can generate strong T cell responses. When it comes to specifically cancer, I think we arrived at a time where we finally had identified mutations that elicit strong T cell responses against cancer. We had a better understanding of how the immune system can prime T cell responses, and how we can design better vaccines; and then further, we had the checkpoint inhibitors, which we knew are absolutely critical to maintain functional T cell response at the tumor site. I think the challenge with this approach is that it's an individualized approach. Most of the mutations that are accumulated in cancer are unique to each patient. So, we need to devise a strategy that allows for designing an individualized, custom-made vaccine for each patient.
Danielle: So, where do you see this going in the future?
Ina: I think a simple answer is vaccines, as a component of combination therapies – I know Lélia has alluded multiple times to how checkpoint inhibitors have been critical to unlocking this field, but I see vaccines as maybe being a foundation of different combinations that can really address lots of different kinds of tumors, and hopefully meet the needs of many patients.
Lélia: Yeah, I think we are still at the beginning of designing potent vaccine understanding, how we can shape the immune response. And there is still a lot to learn about what type of immune response, what kind of phenotype of T cell responses we're really aiming for. Better understanding the T cell response that leads to an effective response is going to be very important. And how we can manipulate or change the platform so that we are generating the immune response, the exact immune response that we are looking for. I think there is still a lot to learn from this point of view.
Danielle: All right. Thank you so much for coming.
Lélia: Thank you. It was fun.
Ina: It was fun.
Stephanie: Hey, Danielle, that was a great discussion. So I want to take this back, because this is a different way of thinking about cancer than when I was in grad school. We used to think about it, you know, one target at a time, you know, one treatment at a time. And we still hear about treatments, new treatments, that are coming on that are successful against certain cancers or for certain people. So where does a cancer vaccine fit into all of this?
Danielle: You know, what I really like about you phrasing the question that way is that I think it still speaks to this idea that as a scientist, we're always trying to look at something that was successful and repeat it and just see. And we kind of sometimes get stuck in these ruts where we're like, this is one strategy we're going to go for. It's going to be the right way.
Stephanie: We just find another target. We just find another target.
Danielle: Yeah, yeah. And it doesn't have to be like that. And actually kind of taking a step back from really pushing for that silver bullet strategy, whether it's chemo, antibody, whatever, that kind of brings us to a place where we can actually take a strategy that reflects the biology that we're going after, which is basically the wild, wild west of mutations. And this is like I'm extremely optimistic about this type of therapy because that is really the strength and it's the ability to have multiple strategies to account for all of the different mutations and variety that are actually present in a tumor.
Wellington: So Danielle, I had a question for you, because when we were as a team researching this, we were all kind of struck with how many theories there are around cancer vaccines, where to approach it, what time to approach it, what target to approach. And also, like, it's been decades and decades. And really, the hallways of science are littered with failures here. What makes you think that this is going to be different?
Danielle: Yeah. Totally littered with failures! But you know what, we learned from them, right? And so, a lot of what we are focused on today is thinking about cancer vaccines as a type of intervention. And I think the reason we're able to get here is that we've had so many advances in sequencing technologies, as well as, even like data mining and data science, to take that information and funnel them into effective decisions for development. So, you know, there are folks, though, that aren't just thinking about now, they're not just thinking about cancer vaccines as an intervention. They're also thinking about them in terms of preventative. I'm not as familiar with that area, but I think that just as data mining and sequencing have really helped, you know, push cancer vaccines as the intervention strategy, I think it's also happening simultaneously with the folks that are thinking of it as preventative. What's going to be really amazing is to see, how are these two different viewpoints going to be feeding off of each other and helping kind of push and drive technologies to get to a more successful treatment option? And honestly, I've lost people to cancer, and I think all of us have known someone in our life that has been touched by this disease. What I'm really hoping for is that 10 years from now, we won't have to be sharing the same kind of heartache. I'm hoping that we're going to have totally different approaches and treatment options, not just as an intervention, but you can only hope for as prevention. And I think that that's the thing that keeps us all going.
And that's our show. Thanks so much for listening. Maria, myself and the whole team are busy looking into new topics for season five. Let us know what you want us to talk about. You can find us at [email protected]. If you haven't already, rate our podcast, it'll help new people find us. And make sure to subscribe to it, so you'll be the first to know when we're back.
And now for me, it's back to stalking cells!