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Three patients fight cancer with genetically tailored vaccines

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Activating dormant cancer-fighting cells

C. Bickel / Science

Researchers are making progress toward a new way to fight cancer, combining genetic sequencing with the power of vaccinations. Genetically tailored vaccines were used to provoke an immune response in three patients with advanced forms of skin cancer, according to a study published in Science today. The study is pretty significant; it’s the first record of a vaccine causing the production of cancer-fighting cells that target specific proteins on the surface of cancer cells in humans.

reminding the immune system that mutated proteins aren't a part of the body

The vaccine approach seeks to "remind" the patient’s immune system that mutated cancer proteins aren't a part of their own bodies, "in a way that will permit the body to fend off newly emerging cancer," explained Elaine Mardis, a co-author of the study and a molecular microbiologist at Washington University, during a press briefing today.

In the study, researchers sequenced the genomes of tumors belonging to three patients with stage III melanoma, as well as the patients’ own genomes. They used those sequenced genomes to identify "neoantigens" — proteins located on the surface of cancer cells — that are uniquely expressed by each patient’s melanoma tumor. This was a challenge, says study co-author and oncologist Beatriz Carreno, because a patient with melanoma can have hundreds of neoantigens on her or his tumor. So, the researchers spent a lot of time trying to figure out which proteins "were more likely to elicit a strong immune response against the tumor."

Eventually, the researchers selected seven neoantigens for each patient. Then, they produced patient-specific vaccines that contained these neoantigens. By including the neoantigens in the vaccine, the researchers sought to activate that immune system and increase the production of cancer-fighting cells. Finally, the researchers administered three doses of the vaccines to each patient over the course of 18 weeks.

a rich pool of tumor-specific immune cells that stay dormant — unless activated by a vaccine

The results are promising. For each patient, the immune system recognized three of the seven neoantigens contained in the vaccines. As a result, patients that received the vaccines produced more cancer-fighting T cells and, more importantly, produced more different kinds of T cells. This is kind of a big deal, the researchers say; it means that cancer patients have a potentially rich pool of tumor-specific immune cells that stay dormant — unless they're activated by a vaccine. "Our team is very encouraged by the quality of the immune response directed against the melanoma neoantigens in all three patients," says Gerald Linette, a co-author of the study and an oncologist at Washington University.

The vaccine appears to be safe; it didn’t cause any negative side-effects. But the technique isn't a cure for cancer. It's more like a cancer-fighting power-up for the human immune system. "The one patient that began the study in remission remains in complete remission with no evidence of cancer," Linette says. "In the other two patients, one had a two-month regression of lung metastases, while the other patient has had stable disease." All the patients appear to be in stable condition at the moment, he added.

Because the study only included three patients, it really only serves to show that this technique is feasible. Researchers will have to conduct more studies in order to determine the treatment’s effectiveness. Still, the scientists are hopeful. The fact that the cells in the vaccine are patient-specific means cause the production of the immune cells that are very "precise in their recognition and elimination of the patient’s own cancer," Linette told The Verge. He thinks the technique could also be used to treat lung cancer, bladder cancer, and colorectal cancer.

"It opens the door to personalized immune-oncology."

The researchers will have to work on making vaccine production more efficient. It took the researchers four months to make these three vaccines. This could be a problem for patients who need a boost right away, so the researchers are working on cutting down the manufacturing time. Eventually, they might be able to make the personalized vaccines in a month.

"It opens the door to personalized immune-oncology," Linette says. The treatment won’t replace current therapies, but it might make fighting off cancer a bit easier. Combining this tailored therapy with other immunotherapies "constitutes a natural progression — one that we will be pursuing in the near future."