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A personalized “cancer vaccine” can help prevent a deadly form of skin cancer from developing for years, a small new study in humans suggests.
contrary to vaccines that prevent infections, such as measles and the flu, cancer vaccines are a form of immunotherapy that destroy cancer cells that already exist. The vaccine train immune cells, called T cells, to better recognize cancer and target it for destruction, while sparing healthy cells in the body.
For example, the experimental new vaccine works by training T cells to spot specific proteins on melanoma cells, a type of skin cancer. In the study, the scientists found that T cells continue to “remember” these proteins for at least four years after vaccination – and they even learn to recognize more melanoma-related proteins over time.
Related: 7 weird things that increase your cancer risk (and 1 that doesn’t)
“The only way this could have happened is if there was indeed a killing of the tumor cells. And it was probably the vaccine-induced T cells that did this killing, ”said study author Dr. Catherine Wu, a medical scientist with the Dana-Farber Cancer Institute and Harvard Medical School in Boston and the Broad Institute in Cambridge, Massachusetts. This is because, once killed, tumor cells break down and spill their contents; The T cells then rush to examine these remains and record this information for future attacks, Wu said.
While the results are promising, the new study only included eight patients, and more trials need to be done to determine exactly how well the vaccine works, she added. But as of now, the limited data suggests the vaccine triggers a persistent immune response and may help keep cancer under control, especially when combined with other immunotherapies, the authors noted.
Personalized vaccines
The new study, published on January 21 in the journal Nature medicine, included patients with advanced melanoma who had recently had surgery for cancer. The researchers took samples of the tumors removed from the patients and used them to make personalized vaccines for each of the eight participants.
“It’s not just about taking something off the shelf, but taking information directly from the patient’s own tumor in order to direct the composition of the vaccine,” Wu said. RNA, a genetic model for proteins inside cells, the team predicted which unique proteins would be built in different cancer cells; these proteins, called neoantigens, act as a red flag for the immune system.
The final vaccines contained segments of these neo-antigens, so patients’ immune cells could learn what they looked like and locate the cancer.
The eight participants each received their personalized vaccine approximately 4 months after surgery, and the team collected safety data for several years thereafter. Patients only experienced mild side effects, such as fatigue and flu-like symptoms, the authors noted. The team also took blood samples at several points in the trial, up to a median of four years after vaccination, to examine patients’ T cell responses.
“What is really striking is the durability of the responses,” said study author Dr. Patrick Ott, medical oncologist at Dana-Farber Cancer Institute, Harvard Medical School and the Broad Institute. “You see persistent responses in all patients treated for several years afterwards,” he said. In addition to being long lasting, responses have diversified over time, meaning that T cells have learned to recognize neoantigens that were not present in the original vaccines.
At the end of the 4-year follow-up period, all eight patients were alive and six out of eight showed no signs of active disease. That said, some experienced cancer recurrence earlier in the study period and received additional treatments.
“From the start, we designed vaccines as a very important adjunct that can be used in combination with other strong agents,” Wu said. In other words, no one expected that vaccines alone completely eliminate cancer in patients. And because several patients received treatment during the trial, the team was able to see whether the vaccine amplified or undermined these therapies.
Two of the patients who received additional treatment stood out in this regard. In both cases, the cancer had spread to their lungs and they were given drugs called “checkpoint blockages,” which essentially tear the brakes off the T cells and help amplify their activity. With the vaccine and the drugs blocking the checkpoints in their systems, the detectable cancer in both patients was quickly ruled out.
“It’s quite unusual to see a complete response right after the initial treatment period… which was the case in both patients,” said Ott. This is an early signal that the vaccine is working with these checkpoint drugs, essentially enhancing the effect of the drugs, he said.
Next steps
In general, only a fraction of melanoma patients benefit from checkpoint blocking drugs, said Dr. Pawel Kalinski, director of cancer vaccine and dendritic cell therapies at Roswell Park Comprehensive Cancer Center in Buffalo, New York. , who did not participate in the study. Other studies have also hinted that cancer vaccines may increase the effectiveness of these drugs, so the new clinical trial adds to that evidence, he said in an email.
That said, “in this small number of patients, [it’s] difficult to draw meaningful conclusions about the effect of checkpoint inhibitors, ”said Dr. Joshua Brody, director of the lymphoma immunotherapy program at Icahn School of Medicine in Mount Sinai, who did not participate under consideration, said in an email. However, logically, “we imagine” that vaccines amplify the effects of these drugs and that such findings should fit into larger clinical trials, Brody said.
Theoretically, vaccines could be given to patients to prime their immune systems and drive T cells to the cancer site; then the checkpoint blocking drugs would come in to kill, Ott said. While it’s not known why some patients don’t respond to checkpoint blockages, on its own, the evidence suggests that drugs work best when T cells are already at the tumor site. Nature News reported; vaccines can therefore help set up the drugs for success. Vaccines and checkpoint blockages could also be associated with various adjuvants – substances that elicit a strong immune response – and substances that support T cell survival, Kalinski said.
But of course, many more trials will have to be done before this future becomes a reality.
“The data presented in this article are certainly very provocative, but relate to relatively few patients whose tumors have been completely resected” by surgery, Kalinski said. Future trials will require a control group – to see how patients who have surgery plus the vaccine sell versus those who have surgery, alone, he said. In addition, scientists will need to determine which T-cell responses are associated with positive long-term results, he added.
In addition, to be practical in medical care, vaccines need to be produced faster than they were in this study, Wu noted. During the trial, vaccine production took between 12 and 20 minutes. weeks; in the future, this process could be streamlined to take just four to five weeks, she said.
Originally posted on Live Science.
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