New Vaccine Improves Survival Among Patients with Melanoma

A new melanoma vaccine has been shown to improve long-term survival among patients when compared to prior iterations of the vaccine, according to recently published research.

Among patients with stages 2B to 4 surgically removed melanoma, the vaccine, developed at UVA Cancer Center, resulted in overall survival (the time a patient lives following treatment) of 74%, 68% and 61% at five, 10 and 15 years, compared with 68%, 56% and 45%, respectively, for the prior version of the vaccine, according to findings published in the journal Nature Communications. Researchers also found that these improved results were also clearer among male patients.

Lead vaccine developer Dr. Craig L. Slingluff Jr., the Joseph Helms Farrow professor of surgery and vice-chair for research in the department of surgery at UVA Health director of the UVA Cancer Center Human Immune Therapy Center, and director of the surgical oncology research training program, discussed these recent findings with CURE®.

CURE: For patients with melanoma, what do you hope is the big takeaway from these findings?

Dr. Craig L. Slingluff Jr.: The main thing that we're excited about is that these data show that patients who received a second-generation vaccine, compared to an earlier version vaccine, have better long-term survival, which is very exciting. It suggests that vaccination against melanoma with some well-defined proteins can be therapeutic and help make people live longer.

What are the basic mechanics behind how these vaccines work?

The idea is to try to stimulate the immune response against protein fragments that are present on the surface of melanoma cells so that the immune system can then recognize those cancer cells and kill them.

The specifics about what we're using are we're actually using peptides rather than RNA or whole proteins, for example. So, they're simple fragments of protein that by themselves should have no toxicity or harm, but they represent what the immune system sees on the surface of the melanoma cells. And we're using a mixture of them so that they can help stimulate a multi-pronged approach. And particular recent data are showing that stimulating not just "killer T cells," but also cells we call “helper T cells” can have a better effect than focusing more on just the killer T cells, basically just trying to stimulate both of the main arms of a cellular immune response against melanoma, rather than just one.

As opposed to some of the other vaccines that have been discussed these are what's known as off-the-shelf vaccines. From a patient’s perspective, what is so exciting and potentially game-changing about an off-the-shelf vaccine?

It's an important point that an off-the-shelf vaccine is ready to use immediately and doesn't require the six to eight weeks’ preparation that at least the current neoantigen vaccines require. So, it can be given without having to wait or do some intervening therapy. This concept of using this kind of off-the-shelf vaccine is not new. But the fact that we have this long-term follow-up data is new, showing benefit for what a lot of people had sort of written off as not being that helpful. So, we're excited that it looks like there really is a benefit in this approach.

One of the other advantages of this off-the-shelf peptide vaccine is that these peptides are very stable. So, you may recall with the COVID vaccines — and obviously, the RNA vaccines for COVID have been game-changing and wonderful — but there were some challenges in getting those vaccines to areas that have limited resources because they need to be kept at like minus 80 degrees centigrade. And so, to hospitals that may not have a freezer that's that cold or if you're trying to ship it to countries that are under-resourced, there are limitations there. But these peptides are really quite stable. And we have data that says they should be stable for like a month even at room temperature.

What is it about melanoma that makes it such an appropriate and appealing target for a vaccine approach?

Several decades ago, when I was just getting started in this area, mostly what we knew was that melanoma was an interesting disease because there were reported cases of melanomas just spontaneously regressing which suggested that the immune system might be active. And then some early findings were encouraging about the response to certain immune therapies.

One of the things that we've become more aware of in recent years because of the ability to study the genetics of cancer cells and other cells much more easily is that there are a lot more genetic mutations in melanomas than many other cancers … and that may make them more recognizable by the immune system.

Not all patients responded to the vaccine equally. In fact, there was a pretty stark divide between male and female patients.

It's really fascinating. I think important to understand differences based on sex, and the National Institutes of Health have been pushing for years for investigators to be sure to include analysis of males and females so that we understand differences in outcome. But I would say that, in general, those sex-related differences have not been appreciated and recognized as much as they probably need to be. And it was a surprise to us to see this big difference. And obviously, we want women to benefit as much as men do. It's just disappointing not to see women benefiting as much but at the same time, it's so important to identify such a difference so that we can focus on understanding why that's happening, which is an area we're very interested in and going forward with.

It is also relevant and interesting that there are other immune therapies — PD1 antibodies fall broadly in the category of immune checkpoint inhibitors, we generally treat men and women pretty much the same in terms of how we make clinical decisions, but as we were aware of these data, I paid a little bit more attention to some of the published data from those trials with the PD1 antibodies. And it's surprising to me, but those studies, for the most part, are pretty consistent in showing that men benefit more from those immune therapies than women do. And it's something that we need to pay more attention to, and to understand, and to try to overcome so that women benefit as much as men.

Transcript edited for clarity and conciseness.

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