Vinod Balachandran
Appearances
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
So cancer vaccines, as you know, have been perhaps one of the most sought-after challenges in medicine. Namely, can you teach the immune system to recognize cancer? And part of the motivation for this has been because vaccines against infectious diseases, viruses, bacteria have been perhaps the most arguably successful medicine to improve health in human history.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
We also know now that the way the immune system recognizes viruses and bacteria is quite similar to how the immune system recognizes cancer. We use the same cells, the same receptors, the same molecules. So if you can do this against a virus or a bacteria, why could this not be possible against cancer? And that it theoretically should be feasible, but perhaps we just don't know how to do it yet.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
The central challenge here, I think, has been the difference between teaching the immune system to recognize something that is intrinsically foreign a virus or a bacteria that the immune system is hardwired to recognize as foreign versus teaching the immune system to recognize something that is self, cancer, or cancer arises from our own tissues.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
The immune system is, in fact, hardwired to recognize, to not recognize ourselves as foreign. So to teach the immune system to recognize cancer S4 requires us to identify the specific proteins that are found in cancers, but not in normal tissues. And to deliver these tumor-specific proteins as antigens, or these are the key critical components that you put in vaccines to make T-cells.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
We had found now about eight years ago by studying rare survivors of pancreatic cancer. So these are approximately 10% of pancreatic cancer patients that received similar treatments as other pancreatic cancer patients, but survived long term.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
What we had found in them through deep scientific analysis is that these patients are able to mount natural T cell responses against their cancers spontaneously, and that these T cells were contrary to the thinking at the time, recognizing mutated proteins in pancreatic cancers, despite pancreatic cancers having very few mutations, which is a common feature of essentially all cancers.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
So this led to this idea that if natural immune responses against a mutation, a ubiquitous byproduct of cancer in pancreatic cancer could somehow impact outcome Could you then replicate this through vaccination in other pancreatic cancer patients?
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
If we teach their immune systems to recognize their cancers in a way similar to what's happening spontaneously in the survivors, could you generate a similar outcome?
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
The reason why we had chosen RNA, this is actually back in 2017, was because these... antigens that these T cells were recognizing in the survivors were mutated antigens that were individual to a patient's cancer. So to vaccinate pancreatic cancer patients and teach their immune systems to recognize their own cancers, what this meant was that vaccine would be
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
need to be created through individual genetic analysis and bespoke vaccine design. And we had felt the best technology for rapid custom cancer vaccination in 2017 was RNA.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
In this trial, we did surgery here on patients at Sloan Kettering in New York. Within 72 hours, we shipped the tumors to colleagues in Germany who then do genetic analysis of the tumor, create a bespoke vaccine, ship it back to us, and then we treat patients here in New York and then watch how the patients do and perform deep scientific analysis in them.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
so we had vaccinated 16 patients in this trial in eight of the 16 patients these vaccines made lots of t cells we call these eight patients responders and in 2023 when we had looked at on average year and a half follow-up we had reported that among the eight responders
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
none of the responders had seen their pancreatic cancers return after surgery and in contrast eight of the non-responders six of eight of these non-responders had seen their cancers return after surgery
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
Yeah, so I think the exciting part of this result is that Prior to this, we were still searching for ways to teach the immune system to recognize pancreatic cancer. And there perhaps was a belief that maybe this was not even possible to teach the immune system to recognize pancreatic cancer because it was too immunologically invisible.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
So the proof of principle that this is not correct and that you can, in fact, teach the immune system to recognize pancreatic cancer, and this is one way to do this, I think is exciting, not only for pancreatic cancer, but also for other cancers, because the manner in which we achieve this in pancreatic cancer, we think can be applied. to other cancers.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
So here, what we examined is whether these T cells made by the vaccine had the ability to persist in patients and retain function in patients. And if they stuck around, do these patients continue to do better? And what we found was that these T cells made by these vaccines appear to have really quite
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
exquisite potential to stick around in patients, which addresses a really fundamental challenge, I think, for cancer vaccines. The average estimated lifespan of these T cells after their vaccination prime and boost was approximately seven years. And not only do they seem to have the potential to stick around, they seem to also continue to work.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
One critical difference here is vaccines against infectious diseases. You have a single pathogen, a virus or a bacteria that infects an entire population. Usually these pathogens are genomically much simpler. You can identify the antigen and then you can make one vaccine to then administer the entire population to then protect the entire population from exposure.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
So their immune system recognizes their individual cancer in a unique way. Although the same cancer may be shared in different patients, meaning... one individual might recognize their pancreatic cancer in a different way compared to another individual recognizing their pancreatic cancer. So a vaccine would have to be individualized
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
And the individualization process at the current moment cannot actually be initiated until patients have the cancer. So at the moment, we would not be able to know how to make, we think, a vaccine to prevent cancer before it in fact occurs, because we actually have to
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
perform genetic analysis of the cancer to understand, oh, this is how this patient's immune system would recognize this individual cancer. Thus, we would have to make the vaccine as such.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
The strategy through which we did cancer vaccination, which required real-time cross-Atlantic transfer of genetic material and drug, does not have to be done this way. This was because this was a foundational effort to do this. And with advances in next-generation sequencing, genetic sequencing can be done on-site or locally. And
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
We also know, and we had always suspected this, which is one of the reasons why we had selected RNA technology for our cancer vaccination platform, RNA can be made extremely rapidly. And this can be done locally, even in countries. local academic or centers of excellence, for instance. So you could envision a scenario where you would not have to send the tumor to location X for genetic analysis.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
genetic analysis and custom vaccine design and manufacture could all be done on site in a very rapid manner compatible with rapid treatment that is required for cancer patients and i think this is a real realistic possibility for scaling individualization
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
That's correct. And that would be one potential application where you could have ready-to-go vaccines for rapid deployment after initial genetic analysis of a tumor. That's one application. You could also envision another application where perhaps there is a library of genetic changes that is particular to a cancer type because
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
these genetic changes that occur in cancer that the immune system can recognize the space is not infinite and it is a finite space so over time as we learn about for example oh pancreatic cancer has these particular types of genetic changes could we create then a library that
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
incorporates these genetic changes into a vaccine that you might perhaps deploy for high-risk individuals for pancreatic cancer, even before they have any signs of cancers occurring. This is, of course, future looking, but I think
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
the learnings that we will now have in secondary prevention will really position us to understand whether such primary prevention efforts, which is really a sort of a holy grail for cancer vaccines, whether we in fact have a path towards that goal.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
We typically think of vaccines and infectious diseases in primary prevention.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
In cancer, here, we are testing these vaccines for secondary prevention, namely patients have a cancer, the cancer is removed, and then we try to use a vaccine to either prevent or delay the cancers from returning after removal. In pancreatic cancer, this feature occurs in approximately 20 to 30% of patients. So this vaccination strategy would be applicable
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
or it was tested in that patient population.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
Yeah, this is an important point to address. And when we look to see, are there other reasons that might explain why the responders are doing better than the non-responders? It's not related to vaccination. we did not find any such differences that could account for that big difference in magnitude that we were seeing in the recurrence rates between the two groups.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
In terms of the immunological differences that you brought up, this was also an important confounder that we addressed, namely Is it possible that the non-responders just had a weaker immune system at baseline? So interestingly, both responders and non-responders also received concurrent vaccination with an unrelated mRNA vaccine, which was SARS-CoV-2 vaccination.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
And turns out that the responders and the non-responders had equivalent immune responses to an unrelated mRNA vaccine. So there was no evidence to suggest that the non-responders just had general weaker immune systems across the board because they were able to make a equivalent immune response as the responders to SARS-CoV-2.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
Yeah. As you mentioned, vaccines have been the most successful medicine in history to improve human health. And I think a hope of the community and a goal of the community has been to try to follow in the footsteps of the successes of our colleagues in developing successful infectious disease vaccines and be able to deploy that against cancer.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
What is the optimal antigen? for a cancer vaccine, namely, how do you teach the immune system to recognize something that is self as foreign? What is an optimal delivery platform to be able to make very strong T cells? Namely, if a patient's immune system has to be taught to recognize each individual cancer individually, meaning you would have to do a bespoke vaccination,
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
Well, what's a platform that could make a bespoke vaccine quickly and strongly, which would be needed for cancer treatment? Number three, what patients could you vaccinate who would have the suitable characteristics to make a lot of immune cells? Unlike prior generations of cancer therapies,
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
which directly kill the cancer cell, chemotherapy or a targeted therapy, vaccines are in fact pro-drugs, if you will. They have to activate cells in the host to generate the response and then fight the cancer. So what optimal hosts would be able to make the cells? And then what are the optimal cells that would then be able to find the cancers and kill them.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
And I think we are in a unique moment, a vaccine moment, where scientific work by the entire community has led to advances where we have potential solutions for all four of these pillars, namely optimal antigens. We now know that
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
Mutations in cancer cells are a highly potent class of clinically relevant antigens, and you can also identify them very quickly through advances in next-generation sequencing. We now have an extremely versatile and safe and potent delivery platform through RNA. So you can find the antigens in the genetic material, and you can make the vaccine very quickly with the RNA.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
So I think that's sort of the moment where we are right now, exciting moment where we have some initial ideas of all of these critical components of an effective vaccine for cancer.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
So I think right now it's also exciting that there are several clinical trials that are currently ongoing that are testing RNA vaccines against patient-specific mutated antigens across a range of cancers. including cancers with very few mutations, such as pancreatic cancer, as well as cancers with many mutations, such as melanoma.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
So essentially spanning the mutational spectrum, which I think will provide the community with a lot of important information on the principles and practice of cancer vaccines across human cancers.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
But I think as a field, we are still in the first generation of cancer vaccines, and there are advances that can be made in terms of vaccine selection accuracy, delivery potency, patient populations that might be more advanced. also suited for cancer vaccines, but perhaps yet undiscovered, as well as other ways to be able to make the cells last for very long periods of time.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
So I think these are all very interesting scientific areas of exploration that the field will be embarking on in the years to come, I'm sure.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
Well, I think we're extremely excited about what we've been observing here in pancreatic cancer, namely that this particular strategy of vaccination is one way to teach the immune system to recognize pancreatic cancer, one of the most challenging cancers in oncology and a cancer that has been historically considered dangerous.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
immunologically invisible and vaccine unsuited so i think we are excited that this approach can in fact teach the immune system to recognize pancreatic cancer and can do so we think at least at this point in time quite well so this can now provide directions on how to apply and test these concepts
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
and extend these concepts for vaccines for other cancer types, as well as other pancreatic cancer patients. So we're very excited to really work hard on all those efforts.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
Thank you so much, Derek. Really appreciate the time.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
Thanks for having me, Derek.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
As you know, pancreatic cancer is now the second leading cause of cancer death in the United States. More cancer deaths from pancreatic cancer than many of the other common cancers such as breast cancer, prostate cancer, ovarian cancer, melanoma, second only to lung cancer.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
Their survival rates for pancreatic cancer in 2025 remain only approximately 10% at five years with our best current treatments, which include surgery, chemotherapy, and radiation. And one of the challenges has been that we've had over the past several decades, many waves of improvements in oncology with waves of oncology drugs, starting with the chemotherapies and
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
Following that, the targeted therapies and more recently the immune therapies and all of these drugs have had greater impact on many of these other more common cancers leading to improvements in outcome. But I think less so for pancreatic cancers.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
After chemotherapy is the next wave of therapies that led to improvements in outcomes for cancer patients with targeted therapies. So this idea that cancers arise from a break in the DNA or a mutation, and this mutation causes a normal cell to become cancerous and then start dividing and replicating uncontrollably. So if you can develop a medicine that selectively blocks
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
the proteins made by this mutation, you can selectively block or kill the cancer cell without affecting the normal cells and thereby having less side effects. And this approach has been very successful in many other cancer types. In pancreatic cancer, when We tried to apply this principle.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
One challenge was the mutation that causes pancreatic cancer to form in the first place is a mutation in this protein gene called KRAS, which for many years has been among the more challenging mutations. genetic mutations to in fact block.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
So when targeted therapies arose and were making waves of improvement in other cancers, we had still not discovered yet a way to apply targeted therapy specifically for pancreatic cancer. So we were lagging behind. After targeted therapies, the next wave of cancer treatments were focused on harnessing our own immune systems to fight cancer.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
And the first way scientists and physicians discovered to do this was through development of a class of drugs called immune checkpoint inhibitors. So these drugs work by boosting immune systems that recognize patients' cancers at baseline. So it's built on the premise that the immune system can recognize cancer, but perhaps not strong enough in people.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
And by boosting these immune cells that recognize patients' cancers with drugs, you can further arm and expand the immune system to recognize patients' cancers. So supercharging your body's natural immune recognition of cancer. Now, this class of medicines were very successful in some cancers, for example, melanoma, lung cancer, but have not been successful in pancreatic cancer.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
Part of the reason for this is because some of these other cancers... immune system is able to recognize cancer much more readily at the outset so it happens more strongly in patients naturally so there are more cells there in cancers thus these cells can be expanded
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
with the drugs if there are too few cells there to begin with it is harder to expand them or perhaps not possible to expand them with these drugs you in fact have to teach the immune system how to recognize the cancer first before you can in fact expand them and that is one way we could try to do this with vaccines.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
So that analogy is correct. I would add to that by saying that in order for the checkpoint inhibitors to work, you need to have enough T cells that are green-lit at the beginning. If you have just one T cell that is green-lit versus 100,000 T cells that are green-lit, this will make a big difference in terms of if you...
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
remove the red light breaks on 100 000 t cells versus one t cell so what we have are slowly learning is that these drugs seem to have um efficacy in cancers where there is much stronger natural immune recognition of cancer So these are cancers such as melanoma and cancer others. So for these other cancers where there could be immune recognition, it's just not strong enough at baseline.
Plain English with Derek Thompson
Can a Vaccine Cure the World’s Deadliest Cancer?
This strategy to remove this red light break, it's not really effective if there's not just enough cells there to begin with.