A personalized “cancer vaccine” may help prevent the growth of a deadly form of skin cancer for years, according to a small new study in humans.
Unlike vaccines which prevent infections such as measles and flu, cancer vaccines are a form of immunotherapy which remove cancer cells that already exist. Vaccines train immune cells called T-cells to better recognize cancer and direct it to destruction, while sparing healthy cells in the body.
For example, the new experimental vaccine works by training T cells to detect specific proteins melanoma cells, a type of skin cancer. In the study, researchers found that T cells continued to “remember”
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“The only way it could have happened was whether there was actually a killing of the tumor cells. And probably the vaccine-induced T cells did this killing,” said study author Dr. Catherine Wu, a doctor-scientist. from the Dana-Farber Cancer Institute and Harvard Medical School in Boston and the Institute of General Science in Cambridge, Massachusetts. This is because once killed, tumor cells disintegrate and spill their contents; T-cells then invade to examine the remains and record this information for future attacks, Wu said.
Although the results are promising, the new study includes only eight patients and more trials are needed to determine exactly how effective the vaccine is, she added. But so far limited data suggest that the vaccine elicits a sustained immune response and may help control cancer, especially when combined with other immunotherapies, the authors note.
The new study, published Jan. 21 in the journal Natural medicine, included patients with advanced melanoma who had recently undergone cancer surgery. The researchers sampled the tumors removed from the patients and used them to make personalized vaccines for each of the eight participants.
“It’s not just taking something off the shelf, it’s actually taking information directly from the patient’s own tumor to direct the composition of the vaccine,” Wu said. Through research RNA, a genetic plan for proteins inside cells, the team predicts which unique proteins will be built into different cancer cells; these proteins, called neoantigens, act as a red flag for the immune system.
The final vaccines contain segments of these neoantigens so that patients’ immune cells can learn what they look like and track cancer.
Each of the eight participants received their personalized vaccines about 4 months after surgery, and the team collected safety data for several years thereafter. Patients had only mild side effects, such as fatigue and flu-like symptoms, the authors note. The team also collected blood samples at several points during the study, up to a median of four years after vaccination, to examine patients’ T cell responses.
“What is really striking is the durability of the answers,” said study author Dr. Patrick Ott, a medical oncologist at the Dana-Farber Cancer Institute, Harvard Medical School and the Institute of General Science. “You see constant reactions in everyone.” treated patients after several years, “he said. In addition to longevity, responses diversify over time, which means that T cells learn to recognize neoantigens that are not present in the original vaccines.
By the end of the 4-year follow-up period, all eight patients were alive and six of the eight showed no signs of active disease. However, some of them had a recurrence of cancer earlier in the study period and received additional treatments.
“From the beginning, we thought of vaccines as a very important adjunct therapy that could be used in combination with other powerful agents,” Wu said. In other words, no one expected vaccines to completely eliminate cancer in patients on their own. And because several patients received treatment during the study, the team can see if the vaccine amplifies or undermines these therapies.
In this respect, two of the patients who received additional treatment stand out. In both cases, the cancer spread to their lungs and they received drugs called “checkpoint blockades” that essentially detached the T-cell brakes and helped boost their activity. With both the vaccine and the blocking drugs in their systems, the detectable cancer in both patients was quickly eliminated.
“It’s quite unusual to see a complete response immediately after the initial treatment period … as was the case for both patients,” Ott said. This is an early signal that the vaccine is working with these checkpoints, boosting the effect of the drugs, he said.
In general, only a fraction of melanoma patients benefit from checkpoints, said Dr. Pavel Kalinski, director of cancer vaccines and dendritic cell therapies at the Comprehensive Cancer Center in Roswell Park in Buffalo, New York, who was not involved in the study. Other studies have also hinted that cancer vaccines may increase the effectiveness of such drugs, so the new clinical trial adds to that evidence, he said in an email.
That said, “with this small number of patients, [it’s] It is difficult to draw significant conclusions about the effect of checkpoint inhibitors, “said Dr. Joshua Brody, director of the Lymphoma Immunotherapy Program at Icahn Medical School in Mount Sinai, who was not involved in the study. However, logically,” we imagine “that vaccines enhance the effects of these drugs and that such findings should be retained in larger clinical trials,” Brody said.
Theoretically, vaccines can be given to patients to prepare their immune system and direct T cells to the site of the cancer; then drugs to block checkpoints will come for the murder, Ott said. Although it is not known why some patients do not respond to blockades at checkpoints, evidence suggests that the drugs work best when T cells are already at the tumor site. Nature News reported; so vaccines can help create drugs for success. Vaccines and checkpoint blockades can also be combined with various adjuvants – substances that provoke a strong immune response – and substances that support T cell survival, Kalinski said.
But, of course, many more trials will have to take place before this future becomes a reality.
“The data presented in this document is certainly very provocative, but it refers to relatively few patients whose tumors have been completely resected,” through surgery, Kalinski said. Future trials will need a control group – to see how patients who have had surgery plus the vaccine are doing, compared to those who have had surgery, he said. In addition, scientists will need to understand which T-cell responses are associated with long-term positive results, he added.
In addition, to be practical in health care, vaccines must be produced faster than they were in this study, Wu said. During the trial, vaccine production took between 12 and 20 weeks; in the future, the process could be streamlined to take just four to five weeks, she said.
Originally published in Live Science.