Pancreatic cancer mRNA vaccine shows promise

We are all aware of Messenger RNA vaccines thanks, largely, to their role in helping to turn the tide against Covid-19. But, before the pandemic had even begun, researchers in New York had been testing the same mRNA vaccine technology as a treatment for cancer. Vinod Balachandran, a surgical oncologist at the Memorial Sloan Kettering Cancer Center, announced they’ve successfully tested a personalised mRNA vaccine for pancreatic cancer. This was administered after the patients had undergone surgery to remove their tumours. So far, half of the trial participants have not seen their tumours return, suggesting the team are on to something…

Vinod - For pancreatic cancer, which is soon to become the second deadliest cause of cancer deaths in the United States. By 2025, there are really no effective treatments. About 88% die with our best current treatments. A rare 12% survive long-term. The reasons why they were able to do this were really unknown.

Chris - It's not just that those 12% present much earlier.

Vinod - That's a good question. And certainly if you have treatment sooner in general, outcomes are better. But this did not completely account for their exceptional long-term outcome as we had compared them to patients who had presented with similar stage and received similar treatments. So our hypothesis was that perhaps there might be some immune activity contributing to their exceptional outcomes.

Chris - If this is an immune effect, what do you suspect then that the immune system would be going after?

Vinod - The immune system we now know recognises cancers. They accumulate genetic errors called mutations. These generate new proteins in these cancers that the human body has never seen before. And this allows the immune system to now recognise these growing cancers as foreign and potentially kill them. So this was an inspiration for our vaccine idea for a clinical trial.

Chris - The idea being that given that you know that in some albeit rare groups of patients, if you make the right immune response, you seem to be able to cure yourself. Can we get the other 88% and persuade their immune system to cure them too with the help of a vaccine?

Vinod - Exactly. So perhaps what is happening in the long-term survivors is the best case scenario, if you will. And can we now try to induce this best case scenario when it does not happen spontaneously by delivering the mutated proteins as vaccines to patients.

Chris - Presumably you therefore had to hunt around and find out in each patient what the constellation of, of mutated altered proteins that their cancer was making were so that you could then harness those as a personalised vaccine for that person's disease.

Vinod - The strongest immune response found in these long-term survivors was specific or targeted towards mutations individual to every single patient's tumour. So to make a vaccine, this indicated that we would need to analyse the genetics of every single patient's tumour, identify the appropriate targets and make a vaccine. So it would be a custom vaccine for every single patient, which of course has its own logistical challenges.

Chris - How did you make the vaccines?

Vinod - We were immediately struck by the unique challenges that we would need to overcome for such a personalised vaccine approach, which would be, number one, you needed a vaccine delivery platform that would be fast because cancer patients require fast treatment. And also a vaccine delivery platform where you could incorporate several targets. And we thought at the time the optimal technology to do this was to use mRNA.

Chris - So presumably what you did was to take the genetic signatures of the tumours from your patients where you could see that there were specific changes in the proteins and take the bits of genetic material as mRNA that corresponds to those and turn that into the vaccine.

Vinod - Right. We started our clinical trial in December of 2019, so this was right before the pandemic. We did surgeries here in New York and within 72 hours we ship the tumours to colleagues in Germany. We then analyse the genetic composition of these tumours and then custom make a vaccine for every single patient and then deliver it back to us here in New York where we give it to patients. And overall, we ended up treating 16 patients with our immune therapies, which included individualised mRNA vaccines.

Chris - And what was the outcome?

Vinod - 50% of the patients who received the vaccines responded. So half.

Chris - How long a follow up do you now have on those responders and are they all still doing well?

Vinod - Right, so the follow-up we have on these patients is 18 months median follow-up. And at this time we find that the responders have not seen their pancreatic cancers come back. In contrast to patients who did not generate an immune response to the vaccine in whom the cancers came back on average about 13 months after surgery. Now this is still a small phase one clinical trial, but we think the results are encouraging and now warrants broader testing in more pancreatic cancer patients going forward.