A four-year-long Phase 1 trial of a personalized skin cancer vaccine has concluded and shows that the vaccine has huge promise in fighting off melanoma over a long period of time. The vaccine, called NeoVax, stimulates the immune system to attack tumor cells in patients with high-risk deadly melanoma. It was successful in bringing about an immune response in all eight patients who received it – all of which survived the trial period, and six of which were disease-free after four years. Personalized cancer vaccines are one of the most promising avenues for battling cancers that take almost 10 million lives each year worldwide. One "cure" for all cancers, in all likelihood, simply doesn’t exist – each cancer is its own cocktail of genetic or environmental factors, presenting different molecules that some therapies may be effective against and some may not. Our best chance at fighting back is most likely personalized therapies or vaccines, which are specifically made for each patient or exact cancer type. To make a vaccine that could combat melanoma, scientists from the Dana-Farber Cancer Institute, Massachusetts, aimed to target antigens that present on the surface of cancer cells. This type of antigen, called a neoantigen, is mutated and only exists on tumor cells – so if the immune system could be taught to recognize and attack them, the malignant cells could be destroyed. NeoVax contains parts of these neoantigens, called epitopes, that initiate an immune response. However, these epitopes need to be tailor-made to the patient, so DNA is extracted for the patient’s tumor and analyzed for the makeup of the epitopes. When the vaccine is injected, T-cells within the body will recognize the neoantigens and remember them, hopefully preventing melanoma development. The study spanned four years, following eight patients with a high chance of melanoma recurrence. Four years after vaccination, all eight patients were alive, with six being completely disease-free. After blood analysis, the researchers discovered their T-cells were responding to melanoma neoantigens, and even other related epitopes as well. “These findings demonstrate that a personal neoantigen vaccine can stimulate a durable immune response in patients with melanoma,” says study co-leader Catherine J. Wu, MD, of Dana-Farber, Brigham and Women’s Hospital (BWH), and the Broad Institute, in a statement. “We found evidence that the initial, targeted immune response has broadened over the years to provide patients with continued protection from the disease.” Of the eight, five patients did see a recurrence of melanoma during the trial which was treated with either surgery or the drug pembrolizumab, an immunotherapy treatment against a variety of cancers. Three of these patients are now disease-free, whilst two saw the cancer spread further. Their results were published in an article to Nature. Whilst the trial is promising on its own, it appears the most effective method of combatting melanoma will be utilizing the vaccine in a multi-treatment approach, tailored to individual cancers. The researchers suggest the vaccine works extremely well with immune checkpoint inhibition, which ensures T-cells can destroy tumor cells. Source
