How A Vaccine Could Treat Pancreatic Cancer

Chuck: This is the Good News About Cancer. I’m Dr. Chuck Ryan.

Alicia: And I’m Dr. Alicia Morgans. 

Chuck: We're oncologists, and we've spent our careers working to understand cancer. We believe that there's more progress now in research and treatment than ever before, and we're here to share that with you.

Alicia: In each episode of this show, we talk with one of our colleagues about a promising development in oncology. We'll break down what's new, why it matters, and how it points the way forward.

Vinod:  We believe these rare survivors of pancreas cancer, their immune systems, are able to recognize their tumors spontaneously in a very strong way that we believe at least, somewhat contributes to their exceptional outcome.  

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Chuck:  So, Alicia, I understand you were on vacation recently. 

Alicia: I was, we had a wonderful family vacation, a great opportunity to explore the world and to spend some time – even if begrudgingly on their end – with the kids. 

Chuck: “Even if begrudgingly on their end,” Hmm. Well, that sounds great. Uh, while you were away, I took the opportunity to talk to one of my new colleagues here at MSK, Dr. Vinod Balachandran. He's working on one of the most difficult problems in cancer: pancreatic cancer. 

Alicia: That is definitely one of our biggest challenges. But while I was away, did you remember that we're talking about the good news about cancer? 

Chuck: Yes, but he's making significant progress in one area of a pancreatic cancer vaccine. 

Alicia: Well, we've definitely talked about vaccines before. How is this one different? 

Chuck: Sure. So we did talk in the podcast before with an epidemiologist who studied the results of the HPV vaccine in cervical cancer. Now, cervical cancer is caused by HPV, which is an infection, it's a viral infection. 

Pancreatic cancer, as far as we know, is not caused by an infection. But many of the mutations in the DNA of a pancreatic cancer tumor are unique to that individual patient. And that creates an opportunity, because when you have this sort of unique barcode of mutations in a particular cancer, it means you can rev the immune system up with a vaccine against that sort of foreign-appearing DNA. And I think what we're going to hear is that he's already done some small clinical trials in patients who've had recent surgery for pancreatic cancer. 

So let's hear my conversation with Dr. Vinod Balachandran. He's a surgical oncologist and is the director of the Olayan Center for Cancer Vaccines at Memorial Sloan Kettering Cancer in New York. 

Alicia: Let's hear it.  

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Chuck: Dr. Vinod Balachandran, welcome to the Good News about Cancer podcast. It's a pleasure to have you. I've been looking forward to this conversation for some time.

 So, uh, you've been doing some really interesting experimental work on a vaccine-based approach to pancreatic cancer. And I think a lot of listeners are gonna wonder: what does- what does that mean? 

Vinod: Yeah, I mean, I think vaccines have been arguably the most impactful medicine in human history. Vaccines against pathogens, infectious diseases, and. The entire oncology community for many decades, essentially last century, have been imagining. Well, how can you make a vaccine against cancer? Could we have the success against cancer similar to the success we have had for infectious diseases? But we have not yet been able to get it done. 

And because right now we know that the immune system recognizes cancer in a very similar way that it recognizes infectious diseases, meaning it uses the same cells, same receptors, same circuits. If you can teach the immune system to recognize the pathogen and have impact, you should theoretically be able to teach the immune system to also recognize cancer.

But I think right now we're sort of in this moment where we have learned how to potentially do this for the first time and actually have potentially an impact. So this is very exciting because really opens up the whole possibility of now making effective vaccines against cancer, not just for treatment, but also in the future, looking for prevention and others. So I think it's a very exciting time.

Chuck: I agree with you. I love putting it in that historical context that after a hundred years of trying, we're now seeing real results in some of the most difficult to treat cancers. 

And you’re right there at the forefront of it, leading studies on vaccines for pancreatic cancer. If you could just walk us through the thought process that led to your work developing the way that it has. 

Vinod: So pancreatic cancer is the second deadliest cancer in the United States in 2026. More cancer deaths from pancreatic cancer than many of the other common cancers such as cancer, ovarian cancer, or prostate cancer, melanoma – second only to lung cancer.

And I think part of the reason for this is because although many of these other cancers have seen waves of improvements in oncology drugs that have led to patients doing better and living longer, pancreatic cancer has not. And the current treatments that we use for pancreatic cancer, which includes surgery, chemotherapy, and radiation, is still largely ineffective. And about 90% of patients with pancreatic cancer, despite these best current treatments, still die of their disease.

So it's fascinating because although 90% die, not everyone does. And a rare 10% of patients survive long term. Why? Unknown. So back in 2015, we wanted to study these rare survivors of pancreatic cancer to try to understand what might be different about them, and could that lead to a way to maybe replicate what's happening in them through other means?

And essentially what we found in this study, first study in 2017, is that we believe these rare survivors of pancreas cancer, their immune systems, are able to recognize their tumors spontaneously in a very strong way that we believe at least somewhat contributes to their exceptional outcome.

Chuck: So tell us how you queried the immune system in those studies. Like, how did you know that?

Vinod: So we take tumors from patients who are these rare long-term survivors. So we assemble a cohort of patients and then we match this cohort to stage, treatment of short-term survivors. So try to minimize any other confounding factors that might lead to misinterpretation and try to really understand, well, what else is going on? 

And what we found was these rare survivors of pancreatic cancer, their tumors have lots of T-cells in them. Now, T-cell is a specialized immune cell in the body that helps the body against viruses and bacteria, and also cancer. And this was interesting because pancreas cancer was thought to be a cancer where T-cells could not really see the cancer very well. 

So the fact that we were seeing lots of T-cells in these rare survivors of pancreas cancer within their tumors suggested, oh, the T cells are maybe seeing something. What is this? And could we now teach other patients’ T-cells to recognize their tumors in a way that's sort of happening spontaneously in these rare survivors?

What we found was that these T-cells were in fact recognizing genetic errors that were present in cancer cells. These are called mutations. So a mutation is a break in the DNA. And the mutation occurs in a normal cell and is what causes a normal cell to become cancerous. 

Chuck:  So we know that pancreatic cancer does not have a lot of oncogenic mutations, or cancer-causing mutations. So these findings around the immune response are pretty significant. How does this knowledge move forward to the idea of a vaccine? 

Vinod: So then what we found was that these mutations that the immune system was seeing in these rare survivors, these were individual to each patient's tumor. So to teach other patients’ immune system to recognize their cancer, for example, with a vaccine, this would require an individualized vaccine. Made for each individual patient because what we were learning was, seems like every person's immune system recognized their cancer in a very unique way. 

This led to this, oh, we have to make these vaccines individualized. And the best technology, we felt, for rapid custom cancer vaccination in the clinic to use RNA. So this is back in 2017 this is before COVID. We approached our biotechnology partners, BioNTech. They were a much smaller company at the time, they had also been treating cancer with RNA-based cancer vaccines, mostly focused on cancers with many mutations, such as melanoma, where we already knew that immune therapies had worked. 

So we proposed to them that although the field might think that pancreatic cancer might be the least-likely cancer for such a vaccine, perhaps is the ideal cancer for all of these reasons. And to their credit, they followed the science and this led to us opening the first phase one clinical trial of RNA vaccines for pancreatic cancer here at MSK. We treated our first patient in December of 2019.

Chuck: So this was the beginning of a clinical trial  you conducted of these vaccines for pancreatic cancer – tell us what you did, and what the outcomes were. 

Vinod: Yeah, in this trial what we did was patients with pancreatic cancer had surgery here at MSK, and then within 72 hours we would ship the tumors to colleagues in Germany. They would do genetic analysis of the tumor and they would custom manufacture a vaccine for each patient and they would send us the drugs back. 

So while this process is ongoing back at New York, we treat patients with an immune therapy. And then once we receive the vaccines, the vaccines, and then chemotherapy. 

There were interesting logistical challenges that we had to contend with because of course, as you know, in March of 2020, we had the COVID pandemic. And this led to clinical and research shutdowns here in New York because we were the epicenter of the pandemic. There were supply chain issues, which was quite important for this trial because it involved real time, cross-Atlantic transfer of patient material and drug, and the slight distraction that BioNTech had now to also make RNA vaccines to save the world from COVID. 

But it was, I would say, a really fantastic team effort between academia and industry, where despite all of these challenges, we were able to not slow the trial down, but we actually accelerated the trial and completed it despite the challenges posed by the pandemic a full year ahead of schedule. 

And what we learned from this clinical trial was that you can actually make a very strong immune response with RNA vaccines against pancreatic cancer, a cancer where historically the thinking was that you could not generate an immune response. 

And the immune response is not only very strong, it also lasts for very long periods of time, and it continues to work after many years. So all of the ideal characteristics for a cancer vaccine, meaning make lots of the cells, they continue to work, and they can stick around for long periods of time.

Chuck: And when you went back to your original work you were talking about, you would look at the tumors, you would see the T-cells, you saw that there were in the long-term, survivors more T cells surrounding the tumor. But now you've taken out the tumor, right, and you've done the surgery. How are you evaluating the efficacy? How are you evaluating the T-cells if you don't have a tumor to look at?

Vinod: So, how do you know that the vaccines are doing anything? Because you're generating immune response, but do we know if they are cancers from coming back? We don't have a clear answer for this yet, because this trial was not designed to answer this question. It was really designed to answer whether the vaccines could be administered safely, whether we could administer it on time, and whether it can generate a strong immune response. The answers to all of those questions were yes, yes, and yes.

So right now there is a larger randomized phase two clinical trial that is global, that is, addressing this question of whether the vaccines could in fact delay or prevent pancreatic cancers from returning after surgery. So this will provide more of a definitive answer.

Chuck: So, agree. There's not a definitive answer on this yet, but your answers in the preliminary work were so provocative. They were published in Nature in February of 2025. So Nature is arguably the leading scientific journal in the world for all science, not just medical science, but for all great innovations. And the headline on that Nature paper was that patients have “long lived T-cells” and I was blown away by the duration of life of some of these T-cells. Tell us about your data.

Vinod: Yeah. What we were interested to look at was you can make an immune response, okay, but for an ideal cancer vaccine, you really want the immune response to stick around. And stick around for a long period of time. So we were interested to try to figure out, well, how long could these T-cells made by the vaccine in fact potentially stick around? 

And what we do is we take the sample, the blood at a very, many time points, and then we sort of track what happens to the T-cells in the peripheral blood over time. And by doing that, you can sort of project into the future, how long we think they would stick around based upon the rate of decay. 

And what we found was that these T-cells could potentially stick around for years. The median estimated lifespan was 7.7 years, and many of these T-cells had an estimated lifespan that even was beyond a decade. So this was very exciting to us because it was just telling us that you can actually make a really strong immune response that can last for very long periods of time against a mutation, a fundamental feature – a fundamental byproduct in fact – of all human cancer. 

And you can do this in pancreatic cancer, a cancer historically thought to not be able to generate an immune response. So this is very exciting because potentially it suggests that you can similarly generate a strong immune response against lots of different cancers in a way. Similar to what we've done in pancreatic cancer.

Chuck: Was there a specific kind of moment, an aha moment when you saw this, or were you just kind of expecting this result? Kind of walk us through your own, if you will, personal response to, to what you saw.

Vinod: Yeah, I mean, I think probably there were two moments. One was the first patient, when we treated – this was in December of 2019– and we had been collecting the blood and essentially performing real-time analysis. And when we observed the immune response in the first patient, what we were seeing was that the T-cells went up to 10% of all T-cells in the blood. So this was a, “Wow that's pretty strong!” moment. And I think that gave us a clear sense that the RNA platform is very potent. 

And a second moment I think was when we at the survival analysis, the recurrence analysis. When we saw that there was a very strong correlation between an immune response and not seeing your cancers come back, even though correlation does not imply causation, and certainly we cannot infer this, it was quite compelling nonetheless, and really sort of spurred us, okay we really have to test this in a broader phase two trial.

Chuck: So your study published in Nature, really interesting results. A key caveat is, is a pretty small number of patients, so there's still work to do.What are the next steps or perhaps the hurdles that one foresees in, in taking it from what you've done at MSK, to something that is more applicable to patients everywhere.

Vinod: Yeah. Well, I think one key point here is, well, if you can make an immune response to pancreatic cancer like this, which is very strong and very potent, the implication here could be: oh, you could also make an immune response against many other cancers, that like pancreatic cancer may not have the best treatments. The high risk cancers. 

So this was one of the motivations for MSK launching the Olayan Center for Cancer Vaccines. The idea here is that academia really has to play an important role in trying to bring these next generation medicines for cancers that are high risk, and this could not be solely left in the realm of industry partners.

So this has been, I think one major area of focus of our group for the past now two years since we launched the center, is to try to work towards developing in-house vaccines at MSK.

Chuck: Well, as we wrap, tell us just a little bit more moving forward, what is it you want to accomplish from here?

Vinod: Well, I think it's a really exciting time for the field, for oncology, for immuno-oncology and cancer vaccinology, because how do you make a vaccine against cancer been a long sought after challenge in modern medical history. And perhaps we are at a moment where we have least some of the required components on how to do this. What is the right antigen? What's the right delivery platform? What's the right clinical setting? And what kind of cells do you need to make? We are sort of at a moment in time we have all of these requisite ingredients for making a good cancer vaccine. 

And I think right now what we really need is urgent testing of these drugs across a broad swath of cancers to see what other cancers and what other clinical settings could these drugs in fact have an impact. And this requires really a concerted effort by academia, industry, federal government, I think, for broad-scale testing, you know, at scale. And I think that would really be the next step.

Chuck: So Vinod Balachandran, it's a real pleasure to talk to you get to know about your work a little bit more, and I think spread the word that what you're doing is, on the way to demonstrating some very, very good news for future cancer patients, who may benefit from this approach. So thank you so much, so much. So thank you so much for joining us on the Good News About.

Vinod: Thank you for having me, Chuck. 

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Alicia: Well, that is incredibly exciting, Chuck. I'm so glad you had the opportunity to speak with him. And my goodness, you're at the same center, both making these amazing advances. It must be really exciting. 

Chuck: Yeah, it was exciting. I think he's really a brilliant person, making great progress. I loved the anecdote he gives of sort of the aha moment when– it was about seven years ago now, they took blood from the first patients who they had been treating and they observed this spike in the T-cell activity in the blood. And they said, you know, it's so much stronger than they expected. And that was sort of the proof of principle that they can activate the T-cells. 

And I think, you know, in cancer in general right now. One of the big headlines, it's not immunotherapy generally it's T-cell activation and we are seeing T-cell activation in a lot of areas. Vaccines will be one, car ts are another, as well as, um, classic immunotherapy activating T-cells and something that we're seeing in our field. This is bispecific T cells. So, uh, all eyes on T-cell right now, and this is really the area of progress. 

Alicia: Well, it makes sense. T cells really are the, the warriors or the soldiers that take things that are not supposed to be in our systems out. So if we can effectively activate them and make sure that they are attacking the things that we want them to get. It sounds like the sky's the limit. 

Chuck: Yep. There's so many things we can keep talking about on this podcast and it's really just so fun to be doing it, uh, with you. And I'm looking forward to all the great good news we have coming, uh, down the pike.

Alica: Well, me too. And to everyone else, thank you for listening to the Good News About Cancer. I'm Dr. Alicia Morgans at Dana-Farber Cancer Institute in Boston.

Chuck: And I'm Dr. Chuck Ryan at Memorial Sloan Kettering Cancer Center in New York. The views we express on this show are our own and do not represent the views or opinions of the institutions where we work. 

Alicia: Thanks to Lilly for support of the show. Our production partner for this series is CitizenRacecar. This episode was produced by Anna Van Dine with post-production by Alex Brouwer. 

Chuck: And there's a whole lot more good news to talk about. So make sure you subscribe to this wherever you listen to your podcasts. And if you like the show, share it with someone you think might find it interesting. 

Alicia: This is the last episode of this season of the good news about cancer – but don’t worry,  we'll be back again soon with some more good news about cancer.