In a groundbreaking study, experts at Dana-Farber/Brigham and Women’s Cancer Center (DF/BWCC) showed that a personalized cancer vaccine, which targets neoantigens, stimulated a potent, safe and highly specific anti-tumor response in six patients with melanoma.
“Our approach addressed the challenges seen with current cancer therapies, including durability of response and corresponding toxicities,” says Catherine J. Wu, MD, a medical oncologist at DF/BWCC, and senior author of the study, which was published on July 13, 2017 in Nature.
All patients were disease-free 32 months after treatment
Six melanoma patients were selected for the study. Each had undergone surgical treatment, but were considered at high risk for recurrence. Vaccinations were administered at a median of 18 weeks after surgery. At a median of 25 months following vaccination, four of the six patients showed no evidence of cancer recurrence. Two patients developed lung metastases and began treatment with pembrolizumab, an anti-PD-1 monoclonal antibody. These two patients had complete resolution of their tumors and remained free of disease. At 32 months following treatment, all patients in the study were free of cancer.
Identifying neoantigens to create the personalized vaccines
To create the personalized vaccines, patients’ tumors underwent whole-exome sequencing to identify somatic mutations. Expression was confirmed by RNA sequencing of the tumor. Algorithms the predicted which neoantigen peptides would bind strongly to the patient’s human leukocyte antigen (HLA) molecules. This process identified dozens of unique neoantigens. Each patient’s personalized vaccine contained approximately 20 of these neoantigens. Due to the vaccines’ highly tumor-specific responses, no serious toxicities were observed.
“Considering the heterogeneity of the tumors, to create a vaccine that would have a long-lasting response we had to use many different tumor-specific neoantigens. A promising strategy will be to combine this approach with other treatments, as we did with the use anti-PD-1 antibodies. We are conducing clinical trials to test these combinations,” says Dr. Wu.