Personal Melanoma Vaccines Evoke Immune Response

In a first-in-people clinical trial, personalized tailor-made melanoma vaccines given to three patients with advanced melanoma appeared to increase the number and diversity of cancer-fighting T cells responding to the tumors. The researchers at Washington University School of Medicine in St. Louis, Mo., developed cancer vaccines by first sequencing the genomes of patients’ tumors and samples of the patients’ healthy tissues to identify mutated proteins called neoantigens unique to the tumor cells. Then, using computer algorithms and lab tests, they were able to predict and test which of those neoantigens would be most likely to provide a potent immune response and would be useful to include in a vaccine. The patients who received the vaccine had had surgery to remove their tumors, but their cancer cells had spread to the lymph nodes, an indicator the deadly skin cancer is likely to recur. The findings set the stage for a Phase I vaccine trial approved by the U.S. Food and Drug Administration as part of an investigational new drug application. The trial will enroll six patients. If testing in this trial indicates the vaccines are effective, they may one day be given to patients after surgery to stimulate the immune system to attack lingering cancer cells and prevent a recurrence.

“This proof-of-principle study shows that these custom-designed vaccines can elicit a very strong immune response,” said senior author Gerald Linette, MD, PhD, a Washington University medical oncologist leading the clinical trial at Siteman Cancer Center and Barnes-Jewish Hospital. “The tumor antigens we inserted into the vaccines provoked a broad response among the immune system’s killer T cells responsible for destroying tumors. Our results are preliminary, but we think the vaccines have therapeutic potential based on the breadth and remarkable diversity of the T-cell response.” The trial was reported on in the journal Science.