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In this episode, Dr. Diane Reidy-Lagunes sits down with two physician-scientists at MSK researching vaccines and novel immunotherapies, Dr. Vinod Balachandran and Dr. Dmitriy Zamarin. They discuss the power of the body’s immune system to prevent and treat cancers, the difference between preventative and therapeutic vaccines, which cancers are treatable with vaccines, and the challenges that lie ahead.
Read more about Dr. Balachandran’s recent research into a vaccine for pancreatic cancer.
Cancer Straight Talk from MSK is a podcast that brings together patients and experts, to have straightforward evidence-based conversations. Memorial Sloan Kettering’s Dr. Diane Reidy-Lagunes hosts, with a mission to educate and empower patients and their family members.
If you have questions, feedback, or topic ideas for upcoming episodes, please email us at: [email protected]
Episode Highlights
What are cancer vaccines? How are cancer vaccines different from other vaccines?
There are two type of cancer vaccines:
- Preventative vaccines are used to prevent cancers from developing.
- Therapeutic vaccines are used to treat existing cancers or prevent cancers from coming back.
Cancer is developed because of breaks in the DNA called mutations. We all have cells with mutations in them that aren’t cancerous, but when multiple mutations occur in the same area, cancer develops.
What makes a cancer vaccine different than a vaccine for a virus or bacteria or pathogen is that cancer is not an invasive, foreign organism that our immune systems can intrinsically detect and attack, as it can for a pathogen (with the simple boost of a vaccine).
Cancer vaccines must teach the immune system to recognize parts of its own cells, and particularly the parts that are slightly different or mutated. This is much more challenging than developing a vaccine for an outside organism.
The critical component of a vaccine is the antigen, which is the protein that teaches the immune system what is foreign and what is not. In most cancers, there is not just one antigen but many, and they are different in every single patient. This is different from vaccines for a virus or pathogen, which only require one antigen in order to be effective in millions of people.
Thankfully, scientists can now identify most individual mutations and have strategies that teach the immune system to recognize these mutations, and therefore the underlying cancer.
Are there vaccines that prevent cancer? Why isn’t there a cancer vaccine?
Certain vaccines for viruses indirectly prevent cancer because viral infections can develop into cancer if left untreated. Hepatitis B and HPV can both cause cervical, head, neck, and anal cancers, as well as others, when left untreated. There are now vaccines for both of these infections which are decreasing the incidences of cancers in those areas.
Aside from cancers that are caused by viruses, unfortunately there is not much yet in terms of preventative cancer vaccines, though there are emerging ideas and data that provide a roadmap to get there.
Most vaccine research focuses on solutions for higher risk populations such as those with an existing genetic mutation who are more likely to develop cancer, and survivors who have had their cancers removed. Developing a vaccine that prevents a cancer from coming back would allow us to better understand how to prevent it in the first place.
Are there vaccines that treat cancer?
There are three classes of therapeutic vaccines being tested: mRNA vaccines, peptide vaccines, and in-situ vaccines.
In-situ vaccines usually involve injecting something directly into the tumor, creating a local inflammation and letting the patient’s immune system decide what is immunogenic versus not, thereby generating an immune response.
- The best example of an in-situ vaccine is one of the oldest cancer vaccines called a BCG, which is a bacterium that treats non-muscle invasive bladder cancer. After a urologist removes the cancer from the wall of the bladder, BCG gets injected into the bladder, tagging any current or future tumor as foreign and enabling it to be recognized by the immune system. There is now even a vaccine for bladder cancer cases that don’t respond to BCG.
- For patients with established metastatic melanoma, a similar FDA-approved viral agent generates an immune response not just in the tumor, but also at the metastatic sites.
How will mRNA be used to treat cancer?
A therapeutic cancer vaccine not only requires many antigens, but also a custom combination of antigens for every patient based on the unique combination of antigens in their tumor. To do this for cancer patients who require treatment fast, technology is required to make a custom vaccine rapidly.
mRNA is ideally suited to do this. Theoretically you can make an mRNA vaccine in as short of time as a weekend. The platform allows you to incorporate multiple antigens into the vaccine for broad, effective coverage, and do so in very little time.
What are the risks of mRNA vaccines? Are mRNA vaccines dangerous?
Since vaccines are in essence the most successful medicine ever made to teach the body to fight infectious disease, it is very exciting that we could tap into this ability and potential of the immune system to fight cancer as well.
Of all the exhausting, often toxic, and painful therapies cancer patients have to endure, vaccines probably have the lowest risks and the best tolerance. At MSK, patients who have been on any cancer vaccine trials usually love the vaccines much more than they have loved chemotherapy, radiation, or anything else that we have given to them. And while vaccines do have some side effects, the dangerous or long-lasting side effects are extremely rare. This is not just true of cancer vaccines, but of any vaccines, including vaccines for the infectious diseases.
MSK recently led a promising clinical trial testing a pancreatic cancer vaccine. What were the results?
Current treatments for pancreatic cancer are not very effective. Nearly 90% of pancreatic cancer patients died within five years of starting treatment despite having received the best available treatments.
Interestingly, 10% of pancreatic cancer patients who receive the same treatments as everyone else have exceptional long-term survival. This is due to a spontaneous and strong immune response to their tumors which is targeting their unique mutations (different in every person).
MSK started a clinical trial in 2019 to test a vaccine that would therapeutically replicate what is happening spontaneously in these long-term survivors. Sixteen patients were given an experimental personalized mRNA vaccine made from their own tumors after surgery, as well as their standard chemotherapy and immunotherapy. Of those, half of the patients did not relapse in an approximate 18-month duration. It’s absolutely amazing. We are now excited to test these vaccines in a broader number of pancreatic cancer patients moving forward.
How will cancer vaccines be used in in the future?
In all likelihood, cancer vaccines won’t replace current treatments such as chemotherapies, targeted therapies, or surgery, but will likely to be added to them.
Hopefully with more positive vaccine trials and a large collection of data, we can utilize A.I. to determine which strategies are better than others so we can go on to design more personalized vaccines.
Show transcript
Dr. Diane Reidy-Lagunes:
Today on the pod: the promise of cancer vaccines. We're already using them to kill viruses that can lead to cancer, such as Hepatitis B, causing liver cancer. But what about using vaccines to prevent cancer that develops from other reasons that are not related to infections or to treat a cancer that's already developed? Let's talk about it.
Hello, I'm Dr. Diane Reidy-Lagunes from Memorial Sloan Kettering Cancer Center, and welcome to Cancer Straight Talk. We're bringing together national experts and patients fighting these diseases to have evidence-based conversations. Our mission is to educate and empower you and your family members to make the right decisions and live happier, healthier lives. For more information on the topics discussed here, or to send us your questions, please visit us at mskcc.org/podcast.
Today I am pleased to be joined by my talented colleagues and friends, Dr. Dmitriy Zamarin, as well as Dr. Vinod Balachandran, who are both physician scientists.
Dmitriy is an oncologist specializing in gynecologic cancers such as ovarian, cervical, and uterus cancers. His clinical and lab research is focusing on developing new ways to use our own immune system to treat and prevent cancer. Vinod is a surgical oncologist who specializes in cancers of the pancreas, bile duct, gallbladder, and liver. His lab research is focusing on finding innovative ways to use our immune system to treat pancreatic cancer, and he led the very first clinical trial testing the use of an mRNA vaccine to do just that. Vinod and Dmitriy, thank you so much for joining us and welcome to the show.
Dr. Vinod Balachandran:
Thank you for having us.
Dr. Dmitriy Zamarin:
Thank you.
Dr. Diane Reidy-Lagunes:
It's so great to see you both. I'm sure most of our listeners are very aware that vaccines can prevent or lessen infection, such as a flu shot or a measles vaccine. But Vinod, can you start off by talking about the different types of cancer vaccines and what they actually do?
Dr. Vinod Balachandran:
Sure. So I think one of the real critical challenges for developing a cancer vaccine has to do with sort of what's fundamentally different in teaching the immune system how to recognize a virus or a bacteria or a pathogen versus recognizing a cancer. Our bodies are pre-programmed to recognize viruses and other pathogens as foreign. So a vaccine to then boost this intrinsic ability of the immune system to recognize these foreign organisms is a little bit easier, since we're using something that's already hardwired into our systems.
Cancer is very different. It is part of ourselves. So in essence, what we have to do is try to teach our own immune system to recognize ourselves, and particularly recognize the parts of the cancers which might be slightly different from ourselves. And this is much more challenging problem than developing an effective vaccine against a virus or a bacteria.
Dr. Diane Reidy-Lagunes:
Absolutely. And so Dmitriy, as we said, we have vaccines that we know can prevent infections, some of which are related to the development of some cancers. But what vaccines do we have now that actually can prevent cancer?
Dr. Dmitriy Zamarin:
You have mentioned that we do have some vaccines that may prevent certain virus infections. And this is probably the best example that I can highlight: vaccines against hepatitis B or more recently vaccines against human papillomavirus or HPV, which causes cervical, head and neck and anal cancers as well as some others. Those have shown to be very effective in preventing virus infection. And this way, indirectly, they can also prevent cancers from development. And we are already seeing impact of these virus preventive vaccines on the incidence of cancers in the areas where the vaccine uptake for these specific viruses has been increased.
Of course, our hope is that with more widespread vaccination against these viruses that cause cancer, we can eventually prevent these cancers from happening in the first place. But we still probably years away from that. But aside from the cancers that are caused by viruses, unfortunately we don't have yet as much in terms of preventative vaccines that we could use, although there are some newer ideas and data emerging that provide suggestions for how we could do that for the broader patient population.
Dr. Diane Reidy-Lagunes:
And just along those lines, in terms of what may be in the pipeline for these preventative types of vaccines, like you said, we have very clear viruses that can lead to cancer. And then we know there are other things that can lead to cancer. What would be an example of maybe a preventative vaccine that's potentially in the pipeline that we could discuss that could potentially prevent the cancer from developing in the first place?
Dr. Vinod Balachandran:
So cancer is developed because of breaks in the DNA called mutations. We can now identify these mutations and then teach the immune system to recognize these mutations as a way to recognize the underlying cancer.
So for prevention, we do have several cancers that develop because these mutations are common and shared between patients. So the same mutation in different people is detected in these cancers. So this allows for possibly developing a vaccine to teach the immune system to recognize this specific mutation that is found in different patients' cancers. But this, as Dmitriy said, is something that we are still in early clinical trials to test these ideas. So we still need a little bit more time to understand exactly what might be the best way to do this. But overall, certainly very exciting times in this field for cancer prevention.
Dr. Dmitriy Zamarin:
The design of vaccines for these types is certainly very feasible. I think it's the execution of these types of studies that would be a challenge because, as you can imagine, we would have to vaccinate probably hundreds of thousands or maybe even millions of people with this soup of vaccine and then follow them over a very long period of time, maybe decades even, to see whether these vaccines are preventative. The idea is fantastic. It's more of a, how can we actually put it to practice?
Now we can potentially focus on the higher risk populations, for example, somebody that has already an existing genetic mutation. And these are the patients that are maybe more likely to develop a particular type of cancer. Maybe if we take these high-risk patients and vaccinate them, we would be able to get a readout earlier. But of course, even those kinds of studies would be very challenging to execute.
Dr. Vinod Balachandran:
Yeah. It's interesting because even though prevention would be the ultimate goal, it may not be the first place, like Dmitriy highlighted, for us to learn how to effectively develop a cancer vaccine.
And it might be more suited in patients who perhaps have already developed cancer and removed the cancers, and then you see whether or not you can generate a vaccine to prevent the cancers from coming back after removing it. And this can then allow us to understand what might be the best way to develop these vaccines, and then you can then move it forward in the prevention.
Dr. Diane Reidy-Lagunes:
Absolutely. And we've talked about this on other episodes, but just to clarify for our listeners, what you're describing is that we all have cells that aren't cancerous per se but have these mutations in them. And we use the analogy of the bingo card where you often need more than one mutation. And then when you have sort of a string of mutations, that's when the cancer develops. So we're talking about one mutation or others that if you can target that in that normal cell with the mutation, perhaps in that patient they're not going to go on to develop that cancer over time. Is that correct to say?
Dr. Dmitriy Zamarin:
That's correct. I can actually take that a little bit further. We know that in certain conditions before you have a cancer, you have a pre-cancerous lesion. I'll give you an example: cervical cancer. Before you get a cervical cancer, you have this sort of a cervical intra-epithelial neoplasia. This is when these are not cancer per se, but they are at a higher risk for becoming cancers. Well, this is actually a perfect opportunity for vaccination to try to see whether it can cause regression or response in these pre-cancerous lesions. And these kinds of studies with vaccines have actually been done and have been shown to be effective. And then there are a number of studies that are ongoing in this setting, specifically this is referring to vaccination against HPV.
Dr. Diane Reidy-Lagunes:
So let's switch gears to therapeutic cancer vaccines. So that's the idea of the cancer develops and now we're going to actually treat it with a vaccine rather than prevent it. And certainly the use of mRNA technology, even before the Covid vaccines, have been tried for this. So Vinod, can you help us explain the mRNA technology and how that might be promising in the world of cancer treatment?
Dr. Vinod Balachandran:
Sure. A lot of this goes back to the initial challenges we outlined with developing a cancer vaccine. For an effective vaccine, the critical component is the antigen. The antigen is the protein that you put in the vaccine to teach the immune system that what you're vaccinating against is foreign. Now in a pathogen, since it's one pathogen – the same virus or bacteria that's infecting the entire population – you can then make one antigen. You put that into a vaccine, you give one vaccine to the whole population, and this can be protective.
In cancers, what we have now learned is that these antigens, there is not just one but there's many potentially in cancers. So you would have to develop a cancer vaccine with many antigens, and these antigens are individual for every single patient. So you would have to custom make a vaccine for every single patient based upon the unique antigens that are found in their tumor.
To do this for cancer patients who require treatment fast, this requires a technology that can make a vaccine rapidly, and mRNA is ideally suited to do this. Theoretically you can make an mRNA vaccine in as short of time as a weekend. It is very quick. The platform allows for you to incorporate multiple antigens into the vaccine. So this really allows for both a fast vaccine and also broad coverage vaccine.
Dr. Diane Reidy-Lagunes:
And in fact, you led the very first clinical trial using mRNA to treat pancreas cancer and were testing this technology actually prior to the Covid pandemic. Could you share with us your research and those findings?
Dr. Vinod Balachandran:
Part of the challenge here for pancreatic cancer is that our current treatments are not very effective. Nearly 90% of pancreatic cancer patients died despite our best current treatments at five years after starting their treatments. It's a really high unmet medical need requiring urgently new ideas.
Interestingly about pancreatic cancer is that there's these 10% of patients who in fact get the same treatments as everyone else, but they have really exceptional long-term survival. These long-term survivors of pancreatic cancer, we believe, are able to generate strong immune responses to their tumors spontaneously. And we also found that these immune responses in these patients' tumors are targeting mutations, which are individual to every single patient's tumor.
So this led us to this idea that, could you then make a vaccine to then replicate, therapeutically, what might be happening spontaneously in long-term survivors? The challenge there was the targets that the immune system was recognizing were individual to every single patient's tumor.
And at the time, we thought the most flexible technology to do this, that can allow for rapid custom cancer vaccination in the clinic, was mRNA. So this was back in 2017 that we started this collaboration between MSK and the then not so well-known biotechnology company BioNTech, to develop mRNA vaccines to treat pancreatic cancer. We started our clinical trial in 2019 and now we have some exciting results which we think are promising. And now we are excited to test these vaccines in a broader number of pancreatic cancer patients moving forward.
Dr. Diane Reidy-Lagunes:
And indeed, this was the first demonstrable success, albeit small numbers, of 16 patients that were given traditional chemotherapy, immunotherapy, as well as the experimental personalized mRNA vaccine made from their own tumors after surgery. Of those, half of the patients did not relapse in an approximate 18-month duration.
I wanted to share in an earlier Cancer Straight Talk episode, we spoke with George Kolasa, who was diagnosed with a glioblastoma in February of 2022. For the past several months, George has actually been traveling to Germany to receive a personalized vaccine. Let's hear more about this from his husband, Justin.
Justin:
The vaccine overall, I mean, it's a relatively seamless process. They extracted peptides from his tumor several months ago, and from that they manufactured a vaccine that matches the peptides that are present on his cancer cells or in his tumor cells. It took them about six to eight weeks to actually make the vaccine. It's only for him. And then it's simply a shot every time we go. They inject the vaccine and then they give an adjuvant afterwards to kind of stimulate the immune system. But the overall goal is to train the immune system to recognize these peptides that are present in the cancer cells to then train the immune system to fight and stop the cancer and prevent future growth. That's our source of hope.
Dr. Diane Reidy-Lagunes:
Vinod, is that similar to the way you conducted your clinical trial?
Dr. Vinod Balachandran:
It's great to hear their experiences. Yes, this is very similar to what we have also been doing with personalized vaccination for pancreatic cancer with mRNA vaccines. So the concepts are very similar, that you make a vaccine based upon a genetic analysis of every single patient's individual cancer as happened in this patient. Right now, there's a few different ways you can potentially deliver these vaccines. We used mRNA technology. This patient seemed like they use a slightly different technology with peptide vaccination, which is also being studied. It's not still clear whether one is better versus the other, but what's exciting is there are several approaches now being tried to teach the immune system to recognize and fight cancer through this individual genetic analysis.
Dr. Diane Reidy-Lagunes:
I will say that for many of our patients that are traveling abroad for this, it's actually quite costly. And so although, as Justin said, it brings tremendous hope, we have to be mindful of the cost that patients may incur for what is still an experimental therapy and not yet proven to be beneficial today.
Dr. Vinod Balachandran:
That's right. The cancer vaccines for these types of indications still remain experimental, which means of course, you know, we don't in fact know if they can work better than existing treatments. And these clinical trials are designed to see if that is in fact true.
Dr. Diane Reidy-Lagunes:
Do you know why some of our patients are actually travelling to Germany as opposed to receiving this therapy in the US?
Dr. Vinod Balachandran:
Yeah, I think there are lots of clinical trials that are happening throughout the world. Different countries have different regulatory requirements as to what patients can receive on clinical trials and what medicines patients can receive off clinical trials. So there are certainly some patients who are able to get some drugs that may not be potentially available in the United States in other countries because they're still being tested in the United States.
Dr. Diane Reidy-Lagunes:
And Dmitriy, clearly the technology is so promising and so exciting, but do we have any approved vaccines for treatment in 2023?
Dr. Dmitriy Zamarin:
We actually do, and we discussed two potential strategies where you can have an mRNA vaccine, or you can have peptide vaccine. And then there's this whole class of vaccines, which is something that I am interested in in my laboratory, called in-situ vaccines. And this is where we're not taking anything out of the patient, we're essentially giving something to the patient, usually something injected directly into the tumor, creating a local inflammation and then letting the patient's own immune system decide what is immunogenic versus not immunogenic and generate an immune response to this.
The best example of this is actually one of the oldest cancer vaccines that has been approved for quite some time, and this is a BCG for treatment of a non-muscle invasive bladder cancer. Bladder cancers, before they invade into the wall of the bladder, they kind of sit there. And these typically get removed by the urologists, but we know that these have a very high risk of coming back. So what has been developed, probably now close to 50 years ago, is a strategy where these patients, after removal of the tumor, get an installation of BCG into the bladder. BCG is a bacterium. It's a bacterium that we used to actually vaccinate people against tuberculosis, but this bacterium generates a local inflammation in the tumor that tags the tumor as foreign and then enables it to be recognized by the immune system.
And in fact, there was another recent similar vaccine that was just approved three months ago for treatment also of bladder cancers that do not respond to BCG. It's a non-pathogenic virus that gets injected into the bladder, and it can result in long-term tumor regressions in these patients.
And finally, for patients that have established metastatic melanoma, we also have an approval of a similar viral agent. You can generate an immune response not just at the tumor, but also at the metastatic sites. Again, just because by doing so, you're kind of teaching the immune system what is foreign and helping it to spread systemically.
Dr. Diane Reidy-Lagunes:
To either of you, where do you think the field is going? I mean, do you see vaccines potentially replacing the traditional therapies that we have today? Adding to it? Only in a certain patient population? I would love to get your thoughts on where you think this may be integrated into the care we provide.
Dr. Vinod Balachandran:
Since vaccines are in essence perhaps the most successful medicine ever made to teach the body to fight infectious disease, we think it is very exciting that we could potentially tap into this ability and potential of the immune system to fight cancer. I don't necessarily think it would be replacing current treatments such as chemotherapies or targeted therapies or surgery, but likely to be added along with them. And this will be some key questions in the upcoming years on what might be the best way to be able to do this so they can really have all these treatments work together.
Dr. Diane Reidy-Lagunes:
Do you think A.I. will help us get there faster?
Dr. Dmitriy Zamarin:
I think A.I. can make anything faster and anything easier. But A.I., which we also call machine learning, requires the data to be put into that machine to actually teach it, right? Hopefully with more positive vaccine trials where we can help to teach A.I. to understand what is the better vaccine, we'll indeed be able to design better vaccines or better personalized vaccines. I think some of the studies that Vinod has reported, these are very exciting, but they're still very early. And to scale it to the larger population, I am sure, A.I. would be something that will become essential.
Dr. Diane Reidy-Lagunes:
So despite the scientific advances and where this field may be going, there's no question that there's a lot of misinformation and a lot of trepidation, if you will, about the idea of mRNA vaccines. Any comments in terms of the risk or concerns you may have?
Dr. Dmitriy Zamarin:
Sure. I'll be honest with you: In cancer, amongst all the types of therapies we give, vaccines probably have the lowest risks and the best tolerance. My patients who have been on any cancer vaccine trials have loved the vaccines much more than they have loved chemotherapy, radiation, or anything else that we have given to them. And while vaccines do have some side effects, the dangerous or long-lasting side effects are extremely rare. And this is not just true of cancer vaccines. This is true of any vaccines, including vaccines for the infectious diseases. So I know that there is a lot of misinformation in the media and unfortunately, these are driven by rare cases that get amplified.
Dr. Diane Reidy-Lagunes:
I think that's right. Well Vinod and Dmitriy, I cannot thank you both enough, not only for being here today, but for being so transformative and using those brilliant brains of yours for helping our patients not only of today or for tomorrow. Keep on going.
Dr. Vinod Balachandran:
Thank you, Diane.
Dr. Dmitriy Zamarin:
Thank you, Diane.
Dr. Diane Reidy-Lagunes:
Thank you for listening to Cancer Straight Talk from Memorial Sloan Kettering Cancer Center. For more information or to send us your questions, please visit us at mskcc.org/podcast. Help others find this helpful resource by rating and reviewing it on Apple Podcasts or wherever you listen. Any products mentioned on the show are not official endorsements by Memorial Sloan Kettering. These episodes are for you but are not intended to be a medical substitute. Please remember to consult your doctor with any questions you have regarding medical conditions. I'm Dr. Diane Reidy-Lagunes. Onward and upward.
