A vaccine that teaches the body to selectively destroy tumors has eluded cancer researchers for decades. Despite many clinical trials, such vaccines have shown little to no success. Now two personalized cancer vaccine approaches appear to have safely prevented cancer relapse in a dozen patients with late-stage skin cancer.
In recent years, scientists have realized that each patient’s tumor harbors a unique set of genetic characteristics, or mutations. So for cancer vaccines to be effective, they’ll probably also have to be unique. Two clinical trials, detailed today in separate papers in Nature, are among the first to show that this might be possible.
In one trial, eight of 13 melanoma patients who got a personalized cancer vaccine were tumor-free nearly two years after being treated. In a smaller study, four of the six patients who received a vaccine had no detectable cancer for more than two years after treatment. All patients had their tumors surgically removed before getting the vaccine.
Fred Ramsdell, vice president of research at the Parker Institute for Cancer Immunotherapy, says the results show it’s possible to use a patient’s own immune system to recognize their specific cancer.
“Essentially, [the study authors] are maximizing the probability of a strong, effective response to proteins found only on the individual patient’s tumor cells,” says Ramsdell, who was not involved in the studies. “It is as if you were being vaccinated against a form of flu that would only infect you.”
The customized vaccines are an emerging class of therapies that take advantage of neoantigens, proteins that appear on tumors and seem to be specific to each cancer patient. To make the vaccines, researchers first sequenced DNA and RNA extracted from each patient’s tumor. They then used computer algorithms to analyze the mutations on each tumor and predict the best targets that code for neoantigens. Based on that data, they created a personalized vaccine containing up to 20 of these neoantigens. Each patient received several injections of the vaccine over a few months.
A handful of companies have recently formed to develop neoantigen-based therapies. Among them are BioNTech, Advaxis, Gritstone Oncology, and Neon Therapeutics, which was founded by Catherine Wu of the Dana Farber Institute, who led the smaller trial unveiled today. Neoantigens are also the focus of a project launched last year by Ramsdell’s institute in San Francisco to figure out the best way to make personalized cancer vaccines.
A type of immunotherapy, therapeutic cancer vaccines are designed to mobilize a person’s immune system against cancer that’s already present in the body. They work similarly to other vaccines, which stimulate a person’s immune system to recognize foreign cells in the body and destroy them. But cancer cells are the body's own cells, making it difficult to “teach” a person's immune system to recognize the cancerous ones. Scientists think making cancer vaccines with neoantigens may be one way to do that.
Cancer researchers are finding out that immunotherapies, including cancer vaccines, don’t work for every patient (see “James Allison Has Unfinished Business with Cancer”). The approach depends on the identification of mutations on a patient’s tumor, Wu says, and the more mutations a tumor has, the better the therapy seems to work.
“We know immunotherapy is successful, but it's only successful so far in patients with tumors that have many mutations,” says Ugur Sahin, an oncologist at the University Medical Center of Johannes Gutenberg University in Germany and CEO of BioNTech, which carried out the larger trial.
In the two trials, researchers designed the vaccines to have multiple neoantigens specific to each patient. Because neoantigens appear only on tumor cells and not on healthy ones, researchers think an injection of neoantigens should look foreign to the immune system and help launch an attack on the cancer cells.
Michel Sadelain, director of the Center for Cell Engineering at Memorial Sloan Kettering Cancer Center, says the results “establish the feasibility of implementing this highly personalized vaccine approach, at least on a small scale.”
Sadelain, who was not involved in the studies, says this high-tech approach looks encouraging, and that improving the computational algorithms could better predict which neoantigens to include to make the vaccines more effective.
One major question about individualized cancer vaccines is whether they’re practical on a large scale. Traditionally, medicines are manufactured in large batches and can be taken off the shelf to treat any patient. Personalized cancer vaccines would need to be tailored to each patient.
Both Sahin and Wu say it took their research teams about three to four months to make each vaccine. They’ve gotten that process down to six weeks or less. Currently, cancer patients begin treatment with traditional therapies about three to six weeks after an initial diagnosis, says Wu. She says her goal is to treat patients with a cancer vaccine in that same window.
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