A personalized “cancer vaccine” can help prevent a deadly form of skin cancer from growing for years, suggests a small study in humans.
Instead vaccines that prevent infections like measles and flu, cancer vaccines are a way of Immunotherapy that eliminate the cancer cells that already exist. Vaccines train immune cells, called T cells, to better recognize cancer and direct it to destruction, sparing healthy cells in the body.
For example, the new experimental vaccine works by training T cells to detect specific proteins in melanoma cells, a type of skin cancer. In the study, scientists found that T cells continue to “remember” these proteins for at least four years after vaccination – and even learn to recognize more melanoma-related proteins over time.
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“The only way it could have happened would be if there were really death of the tumor cells. And presumably it was the vaccine-induced T cells that killed them,” said the study’s author, Dr. Catherine Wu, medical scientist Dana-Farber Cancer Institute and Harvard Medical School in Boston and the Broad Institute in Cambridge, Massachusetts. This is because, once killed, the tumor cells fall apart and spill their contents; The T cells then launch themselves to examine these remains and record that information for future attacks, said Wu.
While the results are promising, the new study included only eight patients, and further testing needs to be conducted to determine exactly the vaccine’s effectiveness, she added. But, as of now, the limited data suggests that the vaccine triggers a persistent immune response and may help keep cancer under control, especially when combined with other immunotherapies, the authors note.
Personalized vaccines
The new study, published on January 21 in the journal Nature Medicine, included patients with advanced melanoma who had recently undergone cancer surgery. The researchers took samples of the tumors removed from the patients and used them to create personalized vaccines for each of the eight participants.
“It’s not just about taking something off the shelf, but getting information directly from the patient’s own tumor to target the composition of the vaccine,” said Wu. Examining RNA, a genetic design for proteins within 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 neoantigens, so that patients’ immune cells could learn their appearance and track cancer.
Each of the eight participants received their personalized vaccine about 4 months after surgery, and the team collected safety data for several years after that. Patients had only mild side effects, such as fatigue and flu-like symptoms, the authors noted. The team also collected blood samples at various points during the trial, up to an average of four years after vaccination, to examine patients’ T cell responses.
“What is really impressive is the durability of the responses,” said the study’s author, Dr. Patrick Ott, an oncologist at the Dana-Farber Cancer Institute, Harvard Medical School and the Broad Institute. “You see persistent responses in all patients treated for several years,” he said. In addition to being long-lived, responses have diversified over time, which means 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 of the eight showed no signs of active disease. That said, some had cancer recurrence at the beginning of the study period and received additional treatments.
“From the beginning, we conceived of vaccines as a very important auxiliary therapy that can be used in combination with other potent agents,” said Wu. In other words, no one expected vaccines, alone, to completely eliminate patients’ cancer. And since several patients received treatment during the trial, the team was able to see whether the vaccine extended or impaired these therapies.
Two of the patients who received complementary treatment stood out in this regard. In both cases, the cancer spread to their lungs and they were given medications called “checkpoint blocks,” which essentially pull the T cell brakes off and help amplify their activity. With vaccine and control point blocking drugs in their systems, the detectable cancer of both patients was quickly eliminated.
“It is 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 sign that the vaccine is working alongside control drugs, basically increasing 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 Vaccines and Dendritic Cell Therapies at Roswell Park Comprehensive Cancer Center in Buffalo, New York, which was not involved in the study. Other studies have also indicated that cancer vaccines may increase the effectiveness of such drugs, so the new clinical trial supplements 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 the Icahn School of Medicine in Mount Sinai, who was not involved in the study, by email. , of course, “we imagine” that vaccines increase the effects of these drugs and that such findings should be maintained in larger clinical trials, Brody said.
Theoretically, vaccines could be given to patients to prepare their immune systems and drive T cells towards the cancer site; then checkpoint blocking drugs would come to death, Ott said. While it’s not known why some patients don’t respond to checkpoint blocks, the evidence alone suggests that drugs work best when T cells are already at the tumor site, Nature News reported; therefore, vaccines can help prepare drugs for success. Vaccines and checkpoint blocks can also be combined with various adjuvants – substances that elicit a strong immune response – and substances that support T-cell survival, Kalinski said.
But it is clear that many other trials will need to be carried out before that future becomes a reality.
“The data presented in this article is certainly very provocative, but it addresses relatively few patients whose tumors have been completely resected” through surgery, said Kalinski. Future tests will need a control group – to see how patients undergoing surgery plus the vaccine do compared to those who undergo surgery alone, he said. In addition, scientists will need to find out what T-cell responses are associated with long-term positive results, he added.
In addition, to be practical in healthcare, vaccines need to be produced more quickly than in the study, Wu noted. During the trial, vaccine production took between 12 and 20 weeks; in the future, this process could be simplified to take just four to five weeks, she said.
Originally published on Live Science.