A Vaccine For Pancreatic Cancer Continues To Show Promise

FLORA LICHTMAN: This is Science Friday. I’m Flora 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 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.

VINOD BALACHANDRIAN: Thank you for having me, Flora.

FLORA LICHTMAN: So why is it so difficult to treat?

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

FLORA LICHTMAN: No, I never think it’s simple when I ask a science question.

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

FLORA LICHTMAN: Do we know why?

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

FLORA LICHTMAN: Right. It upends the assumption that some cancers just can’t be treated with immunotherapy.

VINOD BALACHANDRIAN: 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 our selves 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. And what we have learned over the past few decades is one of the primary ways through which the immune system recognizes a cancer is 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. 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.

FLORA LICHTMAN: So the immune system can spot them.

VINOD BALACHANDRIAN: Exactly.

FLORA 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 from COVID. How is yours different?

VINOD BALACHANDRIAN: 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.

FLORA LICHTMAN: 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.

VINOD BALACHANDRIAN: 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.

FLORA LICHTMAN: And that’s what you did, right?

VINOD BALACHANDRIAN: 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, and within 72 hours, we ship 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.

FLORA 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?

VINOD BALACHANDRIAN: 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.

FLORA LICHTMAN: I hear you saying at the moment, and I’m intrigued.

VINOD BALACHANDRIAN: 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.

FLORA 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.

VINOD BALACHANDRIAN: 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.

FLORA LICHTMAN: That’s what makes them a vaccine, not a drug.

VINOD BALACHANDRIAN: Exactly.

FLORA LICHTMAN: Yeah.

VINOD BALACHANDRIAN: 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.

FLORA 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?

VINOD BALACHANDRIAN: 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, 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?

FLORA LICHTMAN: Did they?

VINOD BALACHANDRIAN: So what we found here is that, surprisingly not only do they stick around, they appear 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 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.

FLORA 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?

VINOD BALACHANDRIAN: So this is a 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. 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.

FLORA LICHTMAN: So you had the– 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?

VINOD BALACHANDRIAN: 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, 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 cancers 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. 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 I– the first phase I clinical trial of RNA vaccines for pancreatic cancer so kudos to that.

FLORA LICHTMAN: Do you see patients?

VINOD BALACHANDRIAN: Yes, I do.

FLORA LICHTMAN: Were any of your patients among the trial participants who had this good outcome?

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

FLORA LICHTMAN: It must be very moving for you. This is such a devastating diagnosis for people to have even a potential new avenue for treatment must feel really profound.

VINOD BALACHANDRIAN: Well, I think watching patients and their families really battle this disease on a daily basis really I think is the greatest inspiration for all of us to really push forth and 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.

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

VINOD BALACHANDRIAN: 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.

FLORA LICHTMAN: Where do you think we’re headed? Do you think we’re going to see a preventative vaccine for pancreatic cancer or a more universal cancer vaccine in your lifetime?

VINOD BALACHANDRIAN: 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 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 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, and I think we have many more exciting advances to come in upcoming years.

FLORA LICHTMAN: Come back and tell us about the results of your phase II trial please.

VINOD BALACHANDRIAN: We would love to do that.

FLORA LICHTMAN: Thank you for taking the time today.

VINOD BALACHANDRIAN: Thank you so much.

FLORA 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.

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