Aaron Schachter: How has the news of this vaccine trial been received in the cancer research community?

Robert Vonderheide: This is a big deal. It’s being greeted with tremendous enthusiasm across the scientific and clinical world. We think the data presented, so far, represents a significant breakthrough that we hope will become a new therapy for patients dealing with melanoma.

Now, as we said, the study found the vaccine reduces the risk of cancer recurrence by 42%. How does it work?

So, this is a vaccine. It is based on the mRNA technology that we’re all familiar with from the COVID-19 era, adapted now to target specific mutations in patients’ melanoma tumors. This is given as a shot, just like a vaccine, and it works by generating an immune response — specifically against those abnormalities in that patient’s tumors — and the immune system now appears to have the power to prevent the recurrence of high-risk melanoma, as you said, more than 42%. It also seems to reduce the chance that melanoma would recur in a distant site, which is also a very important result that we’ve learned from this study.

Which is often how it happens: It pops up in different places, right?

Yes. Recurrence, and recurrence beyond the skin in organs like the liver and elsewhere, is a dreaded consequence that we very much want to prevent in our patients. Now, we have another opportunity to reduce the risk of recurrence even further than we already can.

I saw this being called a “bespoke” or “tailored vaccine.” What does that mean?

It is very interesting. This is not a vaccine sitting on the shelf, one size fits all. This is based on the molecular architecture of each individual’s tumor, which varies from person to person to person. This requires resecting the tumor, sequencing it, understanding the DNA, finding those mutations, and then crafting a vaccine that is just for that person. So, you can imagine this is personalized medicine, at scale.

So, if this can be done for melanoma, can it be done for everything else?

Well, certainly there’s great hope that this technology, having been shown to be effective for patients with melanoma, will be effective for other patients. Already, many clinical trials by a number of companies are testing that hypothesis for patients with lung cancer, bladder cancer, renal cancer. All cancers, to some extent, exhibit these mutations that can be turned on itself as an object of the vaccine. There’s probably a threshold — you need so many mutations — we’re not sure exactly where that is. Not every patient’s tumor can be turned into a vaccine like this across the board, but we are very confident that this, what we’re seeing here, is just the beginning of something great for treating our patients.

I understand that the idea for cancer vaccines has been around for quite a while now. Why are we just seeing these positive results now?

Right. In many ways, you could say the news we heard over the weekend is a 25-year overnight sensation. What it took — and why it took so long — is we, as a field, needed to understand the very basic tenets of how the immune system reacts to cancer, understanding and learning about these mutations, being able to enhance the vaccine with a medicine such as pembrolizumab — which was done in this study — a previous breakthrough for patients with melanoma — to further supercharge the immune response.

Moderna, one of the two companies that announced the results of this study, helped pioneer the mRNA vaccine used during COVID. How much did the pandemic accelerate the development of this technology for treating cancer?

I think we all feel that there’s a direct line between the urgency of the COVID pandemic for the field to understand how to use this new type of formulation for a vaccine, mRNA, show that it’s powerful and safe in the setting of the pandemic, and then returning to an original idea: can mRNA vaccines be used for cancer? So, very much the success of the COVID vaccines by Moderna, and other companies, fuel ongoing efforts to create mRNA vaccines for cancer. Absolutely.

What’s the cost of a single immunotherapy treatment involving this vaccine? Given all the costs of research and development, I imagine it could be quite high.

Yeah, I don’t know. The costs of developing a novel drug in oncology is incredibly expensive. It’s a huge investment, of course. In this particular case, I wouldn’t know exactly, but it is a massive investment to get this done. It’s a massive commitment. That’s why it’s so exciting to see that that investment appears to have paid off.

There are different stages of melanoma; were these patients in any particular stage when they participated in the study?

Two very important features; they were stage 2 or 3, which is not the earliest stages, right? They were more advanced, they’re more high-risk features. The second thing is some of the patients had more advanced disease, but none of the patients had evidence of disease that you might pick up on a CAT scan, or an MRI, or on physical exam. So, all the patients were in remission, which is wonderful. However, we know that some of these patients, such as the ones I just described, are at higher risk of recurrence and that is the event we want to prevent at all costs.

We are talking about a vaccine, as we’ve said numerous times, that prevents the recurrence of melanoma. It’s not like taking the measles vaccine as a child to prevent measles. Can you foresee a vaccine that we would take as children or young people that would prevent cancer?

In some ways, there are such vaccines, such as vaccines against HPV that prevent that infection, which is associated with certain types of cancer. Now, we see an mRNA vaccine being used to prevent recurrence. I think where we’re headed is exactly the hope you’re talking about. Once we understand enough about the immune system and how it grows, will we be able to generate a truly preventative vaccine for all types of cancers? It turns out there’s quite a bit of work ongoing in that area. There’s a number of clinical trials, actually vaccinating healthy individuals who, for some reason, are at risk for cancer. The results, so far, are promising. [There is a] long way to go. It will require more research, but the results that we’ve heard over the last week continue to show that this is real hope. It is something that we, scientifically, may have the ability to go for quite soon.

These results are really exciting and promising, but the vaccine hasn’t yet been approved. What still needs to happen before patients can actually receive it?

The vaccine reported last week remains experimental. The data continues to be obtained, and at some point, and we hope some point soon, the data will be put before regulators to be evaluated for approval. Once it’s approved and manufacturing issues are overcome, then it would become available in a prescribable way, perhaps.