A Vaccine For Pancreatic Cancer Continues To Show Promise

In a small trial, nearly half of pancreatic cancer patients who received an mRNA vaccine for the disease had no relapse three years later.

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• 0:00Speaker 00

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• 0:14Flora Lichtman?

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• 1:04Flora Lichtman?

  This is Science Friday. I'm Flora Lichtman. Today on the podcast, fighting a hard-to-treat cancer with a vaccine.

• 1:12Speaker 02

  This is exciting because we can teach the immune system to recognize other deadly cancers.

• 1:19Flora Lichtman?

  A team at Memorial Sloan-Kettering is developing a new vaccine for pancreatic cancer, which is notoriously difficult to treat. 90% of people who are diagnosed with pancreatic cancer die from the disease, which is what makes a new possible treatment so potentially exciting. A few years ago, the team embarked on a small trial to test the vaccine's safety. 16 patients with pancreatic cancer got it, and even though it was a small study, the results were promising. Half the participants saw an immune response, and in those patients, the cancer hadn't relapsed after 18 months. This week, the team released a new study in Nature, following those same patients, and found that most of them who responded to the vaccine

• 2:01Flora Lichtman?

  in the first study had no recurrence now about three years later. Joining me to talk about these results and what they could mean generally for the future of cancer treatment is Dr. Vinod Balachandran, Associate Attending Surgeon and Director of the Olayan Center for Cancer Vaccines at Memorial Sloan-Kettering, based in New York City. Welcome to Science Friday.

• 2:21Speaker 02

  Thank you for having me, Flora.

• 2:22Flora Lichtman?

  So why is it so difficult to treat?

• 2:26Speaker 02

  So this is an interesting question and you might think it quite simple to answer, but

• 2:33Flora Lichtman?

  No, I never think it's simple when I ask a science question.

• 2:37Speaker 02

  Well, it is deceptively simple, but notoriously still hard for us to answer this. Why is pancreatic cancer in fact so challenging to treat when we've made so much progress in many of the other common cancer types such as breast cancer, prostate cancer, ovarian cancer, et cetera. And as you may know, pancreatic cancer is now the second leading cause of cancer death in the United States in 2025, and second only to lung cancer. Now, one of the reasons is because we have made tremendous progress in outcomes for many of the other more common cancer types, newer waves of oncology drugs, and these

• 3:22Speaker 02

  drugs have had more impact on the other common cancers, but have not impacted outcomes in pancreatic cancer patients.

• 3:32Flora Lichtman?

  Do we know why?

• 3:33Speaker 02

  So the prior thinking had been that perhaps the immune system could not recognize pancreatic cancer because it was perhaps too difficult or too challenging to recognize. And because of that, an immune therapy that would boost immune recognition of cancer would not be effective in pancreatic cancer. So in fact, this is one of the interesting conclusions from some of the work that we have done is that this does not appear to be the case. And you can use vaccination to teach the immune system to recognize pancreatic cancer. So I think this is exciting because

• 4:18Speaker 02

  hopefully this can lead to novel ways through which we can teach the immune system to recognize other high unmet need and deadly cancers.

• 4:26Flora Lichtman?

  Right. It upends the assumption that some cancers just can't be treated with immunotherapy.

• 4:32Speaker 02

  That's correct. The assumption had been that the primary way we think the immune system recognizes a cancer as foreign. As you know, the immune system is hardwired to recognize pathogens such as viruses and bacteria as foreign, and these pathogens are non-self, if you will. Cancers are, however, self. They are derived from our own tissues and the immune system is in fact programmed to not recognize ourselves as foreign. So for the immune system to recognize cancer, you have to teach it exquisitely to recognize the portions of the cancer that are foreign.

• 5:16Speaker 02

  And what we have learned over the past few decades is one of the primary ways through which the immune system recognizes a cancer as foreign is by identifying and recognizing mutated proteins that are found on the surface of cancer cells. So a mutation or a break in the DNA is in fact how a normal cell becomes a cancer cell. The break in the DNA or a mutation causes this normal cell to start dividing abnormally and become cancerous. But through that process, as the cancer cell continues to divide and grow, it accumulates many more of these mutations, so genetic errors.

• 5:57Speaker 02

  And some of these genetic errors produce new proteins and they serve as red flags alerting the immune system that this cell is not behaving properly and needs to be eliminated.

• 6:08Flora Lichtman?

  So the immune system can spot them?

• 6:10Speaker 02

  Exactly.

• 6:11Flora Lichtman?

  Yeah. So I want to talk about the vaccine that you and your collaborators developed. It's an mRNA vaccine and I think many people are familiar with mRNA vaccines, you know, from COVID. How is yours different?

• 6:24Speaker 02

  Right. So a mRNA vaccine for COVID-19, you know the virus. It is the same virus that affects the entire population. Therefore, you can make one vaccine and administer it to the whole population to protect it. But in cancer, since these red flags are individual to each person's cancer, these vaccines for cancer have to be individualized for each patient. So this is a key difference.

• 6:48Flora Lichtman?

  Ah, so the flags are different. You could have the same cancer, but the flags that appear on cancerous cells would be different person to person.

• 6:55Speaker 02

  That's correct. So because the flags are different for each individual and potentially each individual cancer, vaccines have to be individualized for each patient.

• 7:06Flora Lichtman?

  And that's what you did, right?

• 7:07Speaker 02

  And that is what we did for pancreatic cancer. That's correct. In this clinical trial, patients had surgery for pancreatic cancer here in New York City.

• 7:18Speaker 02

  And within 72 hours, we shipped the tumors to colleagues in Germany, where they did genetic analysis of the tumors and then individually made a bespoke vaccine for each patient and then shipped them back to us. And then we began administering their vaccines nine weeks after their surgery. And a feature that allows individualization in a rapid manner is the RNA vaccine technology.

• 7:49Flora Lichtman?

  So you made a vaccine for each individual based on samples of cancerous cells. Does that mean this vaccine only works after you've had cancer?

• 8:02Speaker 02

  So at the current time, we do need to know what the flags are because we then incorporate those flags in an individual vaccine for each patient. So at the moment, we are able to only create a vaccine after we genetically analyze and identify the flags.

• 8:22Flora Lichtman?

  I hear you saying "at the moment," and I'm intrigued.

• 8:25Speaker 02

  Yes, so you could envision perhaps over time, as we accumulate more and more information on the flags, could you then create a library of flags, which could then serve as a basis for a preventative vaccine in the future for an individual cancer? So this remains a hypothesis and something that would be an interesting area of exploration in the future. But for us to learn how to do that, we believe these current vaccines, which are preventing cancers from coming back after they have been removed with surgery, will be a key component to understanding the hows of an effective vaccine for cancer.

• 9:06Flora Lichtman?

  If you could make the vaccine quick enough, could the vaccine also be used as a treatment to wipe out tumors that are that currently exist?

• 9:16Speaker 02

  This is also an important question. Currently, it looks like the vaccines would work best when they are administered to prevent something from occurring or reoccurring.

• 9:28Flora Lichtman?

  That's what makes them a vaccine, not a drug?

• 9:31Speaker 02

  Exactly.

• 9:31Flora Lichtman?

  Yeah.

• 9:32Speaker 02

  Could there be ways we might be able to use it for therapy in the future? It's possible, but as of now, I think this still remains an area of active investigation.

• 9:44Flora Lichtman?

  After the break, what's the future of this approach?

• 9:47Speaker 02

  Could we ever get to vaccines to be able to prevent cancers before they occur? We hope to get there.

• 9:58Speaker 00

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• 11:29Speaker 00

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• 11:31Speaker 03

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• 11:46Flora Lichtman?

  Let's talk about this latest study. You followed these same patients who were in the previous study, who were in this very small trial. What are you reporting this week?

• 11:56Speaker 02

  Right, so in this clinical trial, we vaccinated 16 pancreatic cancer patients with custom vaccines made with RNA. And the goal here in this trial was to teach patients' immune systems to recognize their own individual cancers. And from a broader sense, what do you need for an effective vaccine against cancer? Well, what you need is a vaccine that makes lots of T cells. T cells are specialized immune cells in the body that protect us from infections and cancer. And you need these T cells to stick around in the body for long periods of time and continue to function. So this was a key question that we wanted to examine in these patients,

• 12:41Speaker 02

  namely, could our vaccination strategy, in fact, not only make many T cells, which we had reported earlier in 2023, but do these T cells, in fact, last in these patients? And do they continue to work?

• 12:56Flora Lichtman?

  Did they?

• 12:57Speaker 02

  So what we found here is that, surprisingly, not only do they stick around, they appeared to have the potential to stick around for many, many years. So the average lifespan that we estimated for these T cells was approximately seven years. And in many patients, this number was even higher. So I think the take home from that was that, yes, they do stick around. And yes, they still work. So these are all, we think, have been key barriers for developing effective cancer vaccines. So this was exciting to see that perhaps this particular vaccination strategy

• 13:42Speaker 02

  that we had used is a blueprint to make T cells that last and work and could do so even in the most challenging of cancers.

• 13:51Flora Lichtman?

  I know that this was a Phase I trial. You're looking at, it's small. You're looking at safety. But did you see any direct evidence that these immune cells were actually attacking cancer cells? That they were doing the job you wanted them to do?

• 14:04Speaker 02

  So this is an important question that you're bringing up, namely, are the T cells that are made by the vaccine doing anything? Because in this scenario, we're vaccinating patients when they do not, in fact, have visible cancer. So I think the closest evidence we have for this was that in the patients in whom the vaccines made T cells, three years after surgery, only two of eight of these responders have seen their cancers return. And in contrast, in the other eight patients who received the vaccines, but the vaccines did not make T cells, seven of eight of these patients have seen their cancers return after surgery.

• 14:48Speaker 02

  So these are all correlative pieces of information that are all pointing to the vaccines, perhaps, doing something. But this requires more extensive, larger testing and larger clinical trials. And we have a larger Phase II clinical trial that is currently ongoing to test this exact question.

• 15:07Flora Lichtman?

  So you partnered up with pharmaceutical companies. You mentioned BioNTech to work with you. Was that a difficult sell? How did you convince them to take this risk, given that pancreatic cancer has been so difficult to treat?

• 15:23Speaker 02

  Right. So pancreatic cancer, as I had mentioned to you, historically has been thought of, perhaps, as vaccine unsuited because of the fact that it has very few of these flags. So if you have very few of them, perhaps, why would you pick pancreatic cancer as a cancer to vaccinate against? And we had done some work going back now 2017, where we had examined rare survivors of pancreatic cancer. So these are the rare 10% of pancreatic cancer patients that receive treatments that other pancreatic cancer patients do, but have exceptional long-term survival. And our question really there had been...

• 16:05Speaker 02

  Well, what makes these patients different compared to the other patients? And what we had found in them is that they appear to generate natural immune responses against their pancreatic cancers. So they have T cells that can recognize their red flags in their cancer spontaneously, and this might be impacting their long-term survival. So this was really the motivation for the clinical trial because it raised the question, well, if this is happening in the best-case scenario in the survivors, could you then replicate this with a vaccine? And this is when we approached our colleagues, both at Genentech and Biontech, with this idea to vaccinate pancreatic cancer patients with RNA vaccines.

• 16:48Speaker 02

  And yes, this perhaps was not a very popular idea because pancreatic cancer has a track record of drugs not succeeding, but our work was indicating otherwise. And to their credit, they followed the science, and this led to this phase one, the first phase one clinical trial of RNA vaccines for pancreatic cancer. So kudos to that.

• 17:13Flora Lichtman?

  Do you see patients?

• 17:15Speaker 02

  Yes, I do.

• 17:16Flora Lichtman?

  Were any of your patients among the trial participants who had, you know, this good outcome?

• 17:22Speaker 02

  Yes, I, some of my patients were also on this phase one clinical trial, and this has been a real joy for me to potentially provide them with new options. So I think this, this has been something that really serves as a primary motivation for me to keep trying to make progress in pancreatic cancer patients.

• 17:47Flora Lichtman?

  I mean, it must be very moving for you. I mean, this is such a devastating diagnosis for people. To have even a potential new avenue for treatment must feel really profound.

• 17:59Speaker 02

  Well, I think watching patients and their families really battle this disease on daily basis really, I think, is the greatest inspiration for all of us to really push forth, forge ahead, and really try to make progress. And we're really privileged to be able to take part in these types of clinical trials with their support and participation.

• 18:23Flora Lichtman?

  With a personalized vaccine, is cost going to be a barrier to getting it to patients who need it?

• 18:31Speaker 02

  So I think the hope will be that if we can develop effective vaccines for cancer, personalized or not, this will lead to widespread application across a variety of different cancer types, which would bring down the cost.

• 18:52Flora Lichtman?

  Where do you think we're headed? Do you think we're going to see a preventative vaccine for pancreatic cancer or a sort of more universal cancer vaccine in your lifetime?

• 19:02Speaker 02

  I think these are very intriguing and forward-looking hopes of the community. Could we ever get to vaccines to be able to prevent cancers before they occur? We hope to get there, but I think to get there, we have to focus on the science and really understand how these vaccines might be working in a secondary prevention, namely preventing cancers from coming back after surgery. This will hopefully provide us with important clues on how we might be able to use these vaccines for a primary prevention for pancreatic cancer or even for other cancer types. So I think it's really quite an exciting global vaccine moment that we are in.

• 19:47Speaker 02

  And I think we have many more exciting advances to come in upcoming years.

• 19:52Flora Lichtman?

  Come back and tell us about the results of your Phase II trial, please.

• 19:55Speaker 02

  We would love to do that.

• 19:57Flora Lichtman?

  Thank you for taking the time today.

• 19:58Speaker 02

  Thank you so much.

• 20:00Flora Lichtman?

  Dr. Vinod Balachandran is Associate Attending Surgeon and Director of the Olayan Center for Cancer Vaccines at Memorial Sloan Kettering, based in New York City. And that is about all we have time for. Lots of folks helped make the show happen, including

• 20:17Speaker 04

  George Harper. John Dankosky. Annie Nero.

• 20:21Flora Lichtman?

  Jason Rosenberg. I'm Flora Lichtman. Thanks for listening.