Personalized Vaccine Elicits Responses in Patients With Kidney Cancer

CURE spoke with the principal investigator of a clinical trial evaluating a therapeutic vaccine in advanced kidney cancer: © stock.adobe.com.

Dr. David Braun knows about the potential personalized therapeutic vaccines hold for patients with kidney cancer. Braun was the principal investigator and first author of a trial whose results were published in Nature. According to an announcement from Yale School of Medicine in New Haven, Connecticut, all nine patients with advanced kidney cancer who received such a vaccine had successful anticancer immune responses and were cancer free approximately three years later.

Braun — an assistant professor of medicine at Yale School of Medicine and a member of the Center of Molecular and Cellular Oncology at Yale Cancer Center — sat down for an interview with CURE as part of the “Speaking Out” video series to discuss the trial, its findings and their implications for patients.

CURE: What is the current treatment landscape like for patients with kidney cancer regarding vaccines?

Braun: Kidney cancer vaccines really are still at the experimental phase, meaning they’re still in clinical trials. There’s no vaccine that’s standardly available for kidney cancer that’s approved by any regulatory agency, so they’re still under investigation, and they’re in their early stages. I always want to caution that these are initial studies that have come out, but I would say the initial data is promising. It’s certainly intriguing, and that’s what’s leading to...larger clinical trials to...more rigorously test [whether] these are really effective and...do what they’re supposed to, which is stop kidney cancer from coming back.

You were an author of some study findings published in Nature earlier this year. Can you tell me what you and your colleagues found?

Absolutely, and the background I like to get for this is [two]fold. One is clinical and the other is a little sort of scientific. The clinical part is there really is a need in this particular setting to come up with better treatments, and that setting is people who have a high-risk kidney cancer that still can be removed by surgery, so stage 3 or sometimes even a stage 4, but it’s only [metastasized] in one spot, so it’s still something that can be removed by surgery.

But we know based on history that there’s a high risk of these coming back — maybe a third of patients, sometimes even half of patients, might have their kidney cancer come back. And so there’s a clinical need to come up with new treatments to try to decrease that chance of the kidney cancer coming back.

On the scientific side, we know that immune therapies, medicines that actually use the body’s own immune system to try to fight cancer, have been tremendously successful. They really form a lot of the mainstay of the medicines we use for kidney cancer, but they’re actually very imprecise in their current form. Basically, the way the current immune therapies work is by simply taking the brakes off the immune system so the immune system can become active, and the hope is [that] an active immune system will find cancer cells and get rid of them. But we know it doesn’t always do that. And we think...one of the problems might be that we’re not actually telling the immune system where to go.

The idea of this therapeutic vaccine, meaning it’s used for treatment, it’s not preventive, is essentially adding a steering wheel, or some people have said, adding a GPS. It’s telling the immune system where to go and really steering it in the direction of the tumor. And that’s, I think, a big difference in concept from the way the current forms of immune therapy work.

Given these current findings, what comes next in terms of research?

There were a bunch of questions that we really sought...to try to answer with this current study. This is the first time we ever tried to do this in kidney cancer, which was to make a personalized vaccine, meaning every single patient got a custom-made therapy. We basically took that patient’s own tumor, their individual tumor, and we essentially defined what makes it unique, what is its fingerprint that makes it different from the rest of the body, and that was different for every single patient; every patient has something different that makes their tumor unique. And then, we made a custom vaccine to try to steer the immune system against that custom fingerprint.

So we had a bunch of questions going [in]to the study: Can we even do this for kidney cancer? Is this even feasible to do? Is it actually going to work in the sense that is it going to steer the immune system like we hope it would? And is it going to do so in a way that’s long-lasting and really generates good immune responses? And the answer to all of those [was] yes for this initial study. And I think what was really encouraging is that for this initial study, which was small, it was only nine patients, but those patients were at higher risk of their kidney cancer recurring, and none of those patients had their kidney cancer come back during this study, which was really encouraging to see. But now we have to make sure that it wasn’t just something seen in nine patients, that this really is true at a much larger scale, and that’s what the next study is about.

And so, together with Merck and Moderna, we’ve been involved in a much larger study, a phase 2 study that involves not just nine patients, but hundreds of patients who either get a standard immune therapy called Keytruda [pembrolizumab] or get that same standard treatment, plus the vaccine, and this will be a test at a much larger scale to see [whether] the vaccine is really truly helping to prevent that kidney cancer from coming back. So that’s a study that is now fully enrolled, meaning...about 270 patients have enrolled in the study. And now we have to wait for everyone to get treated, and we have to wait to see the results: Is this some- thing where the vaccine really looks like it’s helping to prevent disease, cancer from coming back?

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