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I compare it to the tricorder in "Star Trek," where they measure some things and they're like, "Let me get back to you tomorrow with an antidote." And they create it, they synthesize it. Amazingly, this is exactly what we're doing. We're saying, "We're going to go and make the medicine for you that is the antidote to that."
-- Dr. Nir Hacohen, Massachusetts General Hospital and the Broad Institute
Martha Pfeiffer knew she was at high risk for melanoma, a potentially deadly skin cancer.
"I had a gazillion sunburns as a kid," she says. "My poor mother tried and tried ..."
In 2012, she felt a new mole on the back of her arm. She didn't think much of it, she says, and didn't go running out to get it checked, "but sure enough, that one turned out to be the one that I got the call about."
The mole was melanoma. Pfeiffer, a writer and editor who lives in Stow, Massachusetts, had surgery to remove the tumor, and the lymph nodes under her arm. A couple of years later, more melanoma turned up, and she had more surgery.
Not an uncommon course of events, so far — but now it gets futuristic. She qualified for a study at the Dana-Farber Cancer Institute that began by taking cells from her tumor to analyze their DNA.
"And then they did a genetic mapping of the cells, and they were able to isolate the mutated cells that were specific to the melanoma," she says. "And from there, that's where the 'cooking' comes in."
The "cooking" uses a scientific recipe that was published recently in the journal Nature: You take those unique tumor mutations, and you use prediction algorithms to choose about 20 of them as likely to be your best targets.
Then, you make a vaccine that trains the patient's immune system to attack only cells with those targets. (The targets are called neoantigens: "neo" because they're new — they exist only on the tumor.) You also add a booster that stimulates the patient's immune response.
"We actually create and synthesize a vaccine just for that individual," says Hacohen, director of cancer immunology at Mass. General and a Broad Institute member. "So that never existed anywhere else in the world, and will never again, because only that person has that cancer."
You then inject the vaccine into the patient's arms or legs multiple times, Hacohen says, and if all goes well, the patient's own immune cells will hunt down the tumor cells that they're now trained to recognize, and wipe them out — even if the cancer has spread.
"When they find the tumor, or any piece of the tumor, they'll start to attack it," he says. "And the hope is to be able to get this vaccine to work strongly enough to completely eliminate the tumor, not just kill a little bit of it."
Familiar vaccines like the shots against measles or chickenpox also train our own immune system to recognize and kill an invader. But this personal vaccine is what's called a therapeutic vaccine — it treats an illness rather than preventing it.
Cancer vaccines are looking more promising. There's been dramatic progress on analyzing tumor DNA, and on treatments that harness the patient's own immune system to fight cancer.
For decades, the quest for a therapeutic vaccine against cancer has frustrated researchers.
Even a couple of years ago, cancer vaccines tended to elicit a resounding "eh" among researchers, says Dr. Catherine Wu of Dana-Farber and the Broad Institute, because "vaccines have been in a tough place."
"When I was a post-doc," she says, "all the literature was about how vaccines didn't work. There were plenty of studies, a lot of dollars that went into clinical trials that could see laboratory evidence of immune responses, but it didn't do anything for the patients."
Now, cancer vaccines are looking more promising. There's been dramatic progress on analyzing tumor DNA, and on treatments that harness the patient's own immune system to fight cancer. (One recent headline: "Cancer vaccines, long considered failure, are hot again.")
Traditional cancer treatments like chemotherapy can cause harsh side effects because they attack healthy cells along with the cancer. But a personal cancer vaccine is so precisely targeted at tumor cells that Martha Pfeiffer says the side effects were no worse than a mild flu.
"I was sitting in the infusion center and always so apologetic to people that I was having it so easy," she says.
Interest Is High, But These Are Very Early Days
Dr. Glenn Dranoff, a longtime leader in cancer vaccine research now at Novartis, says the personal vaccine findings highlight the new power of cancer genetics combined with new insights into the immune system.
"So the work is very scientifically compelling," he says, a novel approach and an elegant proof of concept. "But whether or not that's going to translate into better outcomes for cancer patients is going to require significant more study and clinical testing."
That will take extensive clinical trials. It also remains to be seen how much personal cancer vaccines could cost. Some new cancer treatments run hundreds of thousands of dollars.
"I guess what I would say is the drugs that are out there are costly," says Wu of Dana-Farber. "Our vaccine wasn't more than that, for sure."
Clinical trials are now underway to try this type of personal vaccine for lung and bladder cancer as well as melanoma, she says. It's also being tried for glioblastoma, the brain cancer.
Hacohen, Wu and others have co-founded a biotech company called Neon Therapeutics that has raised more than $160 million to develop the vaccines. Other researchers and companies are also pursuing personal cancer vaccines.
So interest is high, but these are very early days. Pfeiffer was one of just six melanoma patients in the two-year study that was published in Nature, and personal vaccines have only been tried on about two dozen cancer patients overall.
Pfeiffer's scans have remained clear so far, but she has no guarantee the cancer will not recur.
"I'm going on the assumption that this is working," she says, "but people say to you, 'Oh, did the vaccine work?' And my response is, 'You only know if it doesn't work, really!' "
Whatever happens, she is a pioneer patient for a new mode of cancer treatment.
"You're beginning to see how scientists have cracked the code that distinguishes individual cancers and the individual immune system on a patient-by-patient basis," says Jesse Boehm, associate director of the Broad Institute's cancer program.
Historically, cancer has been treated based on the part of the body it comes from, he says, and more recently, based on groupings of patients within a tumor type. But even then, "we know that most patients that look roughly similar don't respond in the same way."
So cancer treatment has to be personal, Boehm says, and the recent progress on personal cancer vaccines shows that it can be: "You can produce a one-of-a-kind drug and deliver it right back to that patient. It's the stuff you would have fantasized about a decade ago."
In fact, Wu and Hacohen were fantasizing about it a decade ago, in many a late-night, husband-and-wife talk about what it would take to really eliminate a cancer, Hacohen says. Now, it's sometime a dinner-table topic with their three kids.
"For example, the first day that we saw an immune response to the first vaccine we gave for the first patient — kind of an exciting time," he recalls. "And of course the kids will be like, 'So you cured cancer?' And we're like, 'No no no no no.'
"We say: 'We just saw the first thing that worked. And here are the additional things we need to happen, and it's going to take a while.' "
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This segment aired on January 8, 2018.
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