Giving melanoma patients a “personalized” vaccine can prompt an anti-tumor immune response that lasts for years, an early study finds.
The study involved just eight patients with advanced melanoma, the deadliest form of skin cancer.
But it builds on earlier work showing it is possible to spur the immune system to respond to an individual’s unique tumor.
All eight patients underwent standard surgery for their melanoma, but were considered high risk for a recurrence. So researchers gave them an experimental vaccine called NeoVax.
Unlike traditional vaccines, it is not a one-size-fits-all jab. Each patient’s vaccine was customized based on key “neoantigens” — abnormal proteins — that were present on their tumor cells.
Even though those proteins are foreign, the immune system is not able, on its own, to generate a major response against them.
“The problem is, the tumor itself doesn’t present enough of a danger signal,” said Dr. Patrick Ott, one of the researchers on the new study.
Beyond that, tumors have various ways of eluding the body’s defenses, explained Ott, of the Dana-Farber Cancer Institute in Boston.
The idea behind NeoVax is to present the immune system with the tumor neoantigens so it can generate a focused T cell response against them. T cells are immune system sentries that can find and destroy cancer cells.
In earlier work, Ott and his colleagues found the vaccine safely activated a tumor-directed T cell response in six melanoma patients. The new study looked at the longer-term response in those patients, plus an additional two who’ve received the vaccine since.
After a typical follow-up of four years, all eight patients were still alive and showing a sustained T cell response to their cancer.
What was “striking,” Ott said, was that the immune response not only persisted, but had broadened: The patients’ T cells remembered the proteins the vaccine had presented, and had “diversified” to recognize other melanoma proteins that had not been included in the vaccine.
The big question, though, is whether it makes a difference in patients’ outcomes.
Five of the eight patients did see their melanoma recur. In two cases, Ott said, the recurrences happened early, and the patients were given drugs called checkpoint inhibitors.
Checkpoint inhibitors, like the cancer vaccine, fall under the umbrella of “immunotherapy” — treatments that enlist the immune system to help destroy tumor cells.
The drugs work by removing the “brakes” from T cells’ ability to respond to tumor cells. And they are already a standard part of care for melanoma patients like those in this study.
When the two study patients with early recurrences started on checkpoint inhibitors, they quickly responded, showing a complete resolution of their tumors. According to Ott, that suggests the vaccine might have worked in concert with the checkpoint inhibitors, generating a T cell response that the medications then freed up.
The only way to know whether the vaccine improves patients’ outlook, however, is through a clinical trial, said Dr. Ahmad Tarhini, a melanoma specialist and researcher who was not involved in the study.
That, he explained, would mean randomly assigning melanoma patients to either have the vaccine added to standard treatment with checkpoint inhibitors, or have standard treatment alone.
Based on these patients, the vaccine by itself might not be enough to prevent melanoma recurrences, said Tarhini, a senior member of the departments of cutaneous oncology and immunology at Moffitt Cancer Center in Tampa, Fla.
That said, Tarhini called the current findings an important step forward in creating customized cancer vaccines.
“As a proof-of-principle, this is successful,” Tarhini said. “The vaccine can induce a durable immune system response that is well-tolerated.”
In theory, Ott said, personalized vaccines could be used for a range of cancers. NeoVax is being studied as an additional therapy for other cancers, including later-stage ovarian and kidney cancers.
If the approach eventually proves to keep cancer recurrences at bay, Ott noted, there will be real-world issues — namely, the time and money it takes to create personalized vaccines.
Dana-Farber, the primary site for the NeoVax research, says it holds “a proprietary and financial interest in the personalized neoantigen vaccine.”
The study was published Jan. 21 in Nature Medicine.
The American Cancer Society has more on cancer immunotherapy.
SOURCES: Patrick A. Ott, MD, PhD, clinical director, Melanoma Disease Center, Dana-Farber Cancer Institute, associate professor, medicine, Harvard Medical School, Boston; Ahmad Tarhini, MD, senior member, departments of cutaneous oncology and immunology, and director, cutaneous clinical and translational research, Moffitt Cancer Center, Tampa, Fla.; Nature Medicine, Jan. 21, 2021, online
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