For decades now, the prospect of personalized cancer vaccines has tantalized medical scientists. Studies in lab mice were perpetually encouraging. But there was no proof with humans. Now the most impressive evidence yet suggests that this long-awaited form of immunotherapy may actually work in some patients.
“Cancer vaccine” might seem like a surprising term for this treatment, since it doesn’t prevent a person from getting the disease and each shot has to be customized. But like any vaccine, it summons the immune system to attack a dangerous foe. To develop the vaccine, researchers analyze neoantigens—protein fragments on the surfaces of cancer cells—and look for the specific mutations that created them. Then they use a computer algorithm to determine which peptides have the best chance of activating that person’s immune system to fight the cancer. Making the vaccine in a lab takes about three months.
One of two groundbreaking studies published last year involved six patients at Harvard’s Dana-Farber Cancer Institute. All six had recently had melanoma tumors removed and were at high risk of recurrence. They were given vaccines that targeted up to 20 neoantigens from their cancer cells. Their immune systems took notice. “Importantly, we could show that there was recognition of the patient’s own tumor,” says Catherine Wu, a Harvard oncologist who co-authored the study.
One of those patients (who remains anonymous) had her first melanoma removed from her left arm in November 2012. Two years later, the cancer returned. This made it likely that it would continue to metastasize, possibly throughout other parts of her body. Instead of getting chemotherapy or radiation, she entered the Dana-Farber trial. Two and a half years after her personalized vaccine therapy, she remains tumor free without further treatment. Three other patients in the study made similar progress. The other two became tumor-free after the vaccine was paired with a checkpoint inhibitor.
The second study, at the Johannes Gutenberg University of Mainz in Germany, involved 13 subjects with recently removed melanomas. Five of them developed new tumors before their vaccines were ready, but two of them saw those tumors shrink while receiving the vaccine. A third went into complete remission after starting a checkpoint inhibitor medication. The eight patients who had no visible tumors when the vaccinations started were still recurrence-free more than a year later.
Strikingly, none of the patients in either study experienced adverse effects apart from fatigue, rashes, flu-like symptoms or soreness at the injection site. Unlike other immunotherapies, which manipulate T-cells and can trigger autoimmune complications, cancer vaccines prompt the immune system to make its own T-cells that target only the cancer.
Patrick Ott, another author on the Dana-Farber study, hopes new technologies will make it easy to build these vaccines inexpensively, and within a few days. He’s confident that the first two trials will inspire rapid progress: “If you show a good response, the industry is going to jump on it and make it even better.”