Q&A: Could a new melanoma vaccine change cancer treatment?
· Medical Xpressby Traci Hale, University of Virginia
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A personalized melanoma vaccine, called intismeran, could mark a major advance in cancer treatment. Last week, pharmaceutical companies Merck and Moderna announced clinical trial results showing the vaccine, combined with immunotherapy, reduced the risk of cancer returning or death by 42% compared with immunotherapy alone.
Dr. Craig Slingluff, a UVA Health researcher who has spent decades developing cancer vaccines, says the findings offer new hope for helping more patients live longer and potentially curing some cancers.
He spoke with UVA Today about how the vaccine works, what it means for patients and why he is optimistic about the future of cancer treatment.
How significant is this announcement in the fight against melanoma?
This is a significant finding in melanoma treatment and in the broader field of personalized cancer therapies. It is the first randomized trial testing a personalized mRNA vaccine for cancer that has shown meaningful and significant benefit for patients.
The side effects were very tolerable, so the data show a high benefit-to-risk ratio. The success here shows that a personalized approach built on the mRNA platform that worked so well for COVID vaccines can be successful and may well lead to similar benefits for other cancers.
The study found the vaccine reduced by 42% the risk of return of melanoma. How much of an improvement is it over current treatments?
The trial was designed to compare the benefit of adding the vaccine to the current standard treatment. Standard treatment after surgery for melanoma is an immunotherapy called pembrolizumab (or a similar antibody to nivolumab). Both pembrolizumab and nivolumab are antibodies to the PD-1 molecule. So the study showed a 42% reduction in recurrence compared to current treatments. This means the chance of recurrence can be expected to be 42% lower than if they took pembrolizumab alone.
Most people think of vaccines as preventing diseases. How does this cancer vaccine work, and what makes it different from a traditional vaccine?
Cancer vaccines are similar to all vaccines in that they are designed to stimulate immune responses. However, most vaccines against infections are designed to stimulate antibody responses to the virus. For cancer vaccines, however, the main goal is to induce immune cells in the blood to attack the cancer cells.
There is hope, eventually, to be able to give vaccines to prevent melanoma (and other cancers), but for now, the goal is to prevent recurrence or spread of melanoma.
The vaccine is personalized for each patient. How do scientists create a vaccine based on someone's cancer, and why is that important?
This vaccine builds on two major scientific advances: sequencing of the human genome and mRNA technology that had been developed for COVID-19.
Basically, DNA from a biopsy of the patient's melanoma is evaluated and sequenced, then compared with DNA from normal tissues (like blood cells). This enables the identification of genetic changes (mutations) specific to melanoma. Some of these are identified as likely to be recognized by the immune system. Up to 34 of these were selected for each patient. RNA encoding those targets is then synthesized and encapsulated in nanoparticles for patient administration. This took about two months to make on average.
Who could benefit from this vaccine? Could it eventually help people with other types of cancer?
This vaccine was tested in patients who had surgery to remove all known melanoma but were at high risk of recurrence. This included patients with thick melanomas without known spread (stage IIB-IIC) and those with spread to lymph nodes (stage III) or distant sites (stage IV) that were removed surgically. Benefit was seen across all those stages of melanoma. Thus, a broad population of patients could benefit.
It is notable, though, that about 20% of patients enrolled in the trial were not able to get the vaccine, mostly because of insufficient tumor biopsy material. However, the technology for making the personalized vaccine was successful in most.
Yes, it could eventually help people with other types of cancer; clinical trials are underway.
How soon might this vaccine become available to patients? What still needs to happen before doctors can begin using it more widely?
We don't know exactly, but I think most investigators and clinicians in this field expect that the FDA will approve this vaccine for melanoma soon—perhaps as early as 2027.
UVA has a long history of melanoma research, including your own work. How does this announcement build on that research, and what excites you most about the future of cancer treatment?
We have been working on identifying immune targets (antigens) on melanoma and on vaccinating against them. Whereas this Merck/Moderna vaccine is personalized for each patient, ours is designed to be useful across all patients, so that it can be given immediately when patients need it. We have recently published data supporting improved long-term overall survival among patients who received our second-generation melanoma vaccine compared with our first-generation vaccine, with a 36% reduction in mortality.
I believe that a hybrid vaccine targeting common melanoma antigens as well as personalized antigens is ideal. In particular, for melanoma, patients receive pembrolizumab as soon as possible, and there is some evidence that vaccines may work better if they are started at the same time. The personalized vaccines take time to prepare, and not all were made successfully. Our vaccine can be started at the same time as pembrolizumab, and intismeran could be added later, when available.
One of our current directions is to test an enhanced off-the-shelf vaccine (OncoBlend33) in this setting. We will also test whether directly injecting the vaccine into cancers before surgery (in combination with PD-1 blockade) can enhance T cells' ability to infiltrate and destroy them.
Our team is in discussions with the leadership of (UVA's) Paul and Diane Manning Institute of Biotechnology to guide the development of our cancer vaccines in light of this exciting news, which supports the promise of cancer vaccines more broadly.
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