A personalized, long-peptide vaccine that can target up to 20 personal neoantigens per patient has been successful in preventing melanoma in patients at high risk for recurrence, according to the findings of a phase 1 study published in Nature Medicine.1 The vaccine helps the body mount a robust response to the disease by training a patient’s immune system to recognize and attack cancerous signals, with increasing detection over time.
“This really hasn’t been shown before,” said Patrick Ott, MD, a co-author of the study and a medical oncologist at Dana-Farber Cancer Institute in Boston, Massachusetts. “Nobody has looked at responses that are going out this far, and it’s definitely very reassuring and encouraging to see that these responses are durable and persistent.”
The study included 8 patients who had undergone surgery to treat advanced melanoma and were considered at high risk for disease recurrence. All patients received the neoantigen vaccine at a median of 18 weeks after surgery. At a 4-year follow-up, all 8 patients were alive, with 6 showing no signs of active disease.
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To design the personalized vaccine, researchers scanned DNA from each patient’s tumor to reveal the specific epitopes present on the surface of the melanoma cells. The neoantigen vaccine not only spurred each patient’s T-cells to attack the epitopes present in the vaccine but also to attack other epitopes associated with melanoma, as well.
Two patients were found to have cancer cells that had metastasized to the lungs prior to receiving the neoantigen vaccine. These patients received immune checkpoint inhibitors in addition to the vaccine. Results showed that, although active disease had not been eliminated, the vaccine had still propelled T-cells to invade the tumor tissue and attack melanoma cells.
“It is interesting to see these responses because it demonstrates the vaccine’s impact on the tumor,” said Dr Ott, adding that the results do not show T-cells “learning” so much as being drawn to an antigen that they have been trained to attack but were not able to efficiently recognize the presence of prior to vaccination.
“The vaccine could be used alone in lower-risk patients to avoid the toxicities seen with immunotherapy,” said Beth Buchbinder, MD, another study co-author and a medical oncologist at Dana-Farber. She also believes that the vaccine should be paired with immunotherapy. “Since the vaccine appears to be training the immune system to respond to melanoma cells, it could also be used with immunotherapy in the advanced melanoma setting to treat patients with unresectable disease.”
Reference
Hu Z, Leet DE, Allesøe RL, et al. Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma. Nature Medicine. Published online January 21, 2021. doi:10.1038/s41591-020-01206-4
