Early data from a “first-in-people” clinical trial at Washington University School of Medicine in St. Louis, MO, suggests that personalized melanoma vaccines may provide a powerful immune response against tumor mutations.
Such vaccines have been attempted before, but they have worked by targeting proteins expressed at high levels in certain cancers – the problem with this approach being that the same proteins can also be found in healthy cells. As such, it is difficult to provoke a strong immune response with this method.
The new vaccines were created by first sequencing the genomes of the patients’ tumors, as well as samples of healthy tissues from the patient, so that mutated proteins called neoantigens – which are unique to tumor cells – can be identified.
Computer algorithms and laboratory tests were then used to predict which neoantigens would be most likely to cause a potent immune response that could be used in a vaccine.
“You can think of a neoantigen as a flag on each cancer cell,” explains first author of the study Beatriz Carreno, associate professor of medicine. “Each patient’s melanoma can have hundreds of different flags. As part of validating candidate vaccine neoantigens, we were able to identify the flags on the patients’ cancer cells. Then we created customized vaccines to a select group of flags on each patient’s tumor.”
Three patients with advanced melanoma received these vaccines. After receiving the vaccines, blood samples were taken from the patients every week for 4 months. The researchers found that each patient had an increased number and diversity of T cells fighting the tumors.
According to the researchers, the vaccine’s stimulation of T cell clones suggests that this approach may be useful in activating a range of T cells that can target mutations in lung cancer, bladder cancer or colorectal cancer, which are other cancers with similarly high mutation rates to melanoma.
The patients had previously had surgery to remove their tumors, but cancer cells had spread to their lymph nodes, which often predicts a return of melanoma.
“This proof-of-principal study shows that these custom-designed vaccines can elicit a very strong immune response,” says senior author Dr. Gerald Linette, a Washington University medical oncologist leading the clinical trial at Siteman Cancer Center at Barnes-Jewish Hospital in St. Louis. Dr. Linette adds:
“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.”
Due to the success reported so far, a phase 1 vaccine trial has now been approved by the Food and Drug Administration (FDA) that will enroll six patients. If testing in these patients confirms the vaccines to be effective, then the vaccines could one day be used to stimulate an anticancer immune attack following surgery. These immune attacks could seek out and destroy any remaining cancer cells, preventing recurrence.
However, the researchers caution that it is too early to say whether the vaccines will be effective in the long term, as the study was designed to assess safety and immune response. However, none of the trial participants have experienced adverse effects from their personalized vaccines.
“Our team has developed a new strategy for personalized cancer immunotherapy,” Dr. Linette says.
“Many researchers have hypothesized that it would be possible to use neoantigens to broadly activate the human immune system, but we didn’t know that for sure until now. We still have much more work to do, but this is an important first step and opens the door to personalized immune-based cancer treatments.”