A personalized ‘cancer vaccine’ could help grow a deadly form of skin cancer for years, a small new study among humans has suggested.
Other than vaccines which prevent infections, such as measles and influenza, cancer vaccines are a form of immunotherapy which decreases cancer cells that already exist. The vaccines practice immune cells, called T cells, to better recognize and destroy cancer while sparing healthy cells in the body.
The new experimental vaccine works, for example, by training T cells to detect specific proteins melanoma cells, a type of skin cancer. In the study, scientists found that the T cells still “remember” these proteins at least four years after vaccination – and they learn to recognize even more melanoma-related proteins over time.
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“The only way that could have happened was if the tumor cells had died. And presumably it was the T cells induced by the vaccine that did the killing,” said Dr. Catherine Wu, a doctor-scientist at the Dana-Farber Cancer Institute and Harvard Medical School in Boston and the Broad Institute in Cambridge, Massachusetts. This is because tumor cells, after being killed, fall apart and spill their contents; T cells then move in to investigate this surplus and sign off the information for future attacks, Wu said.
Although the results are promising, the new study included only eight patients, and more trials need to be done to determine how effective the vaccine is, she added. But from now on, the limited data suggest that the vaccine elicits 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, which appeared in the journal on January 21 Physical Medicine, included patients with advanced melanoma who had recently undergone surgery for the cancer. The researchers took samples of the patients’ removed tumors and used them to make personalized vaccines for each of the eight participants.
“It’s not just to take something off the shelf, but to take information directly from the patient’s own tumor to guide the composition of the vaccine,” Wu said. By investigating RNA, a genetic blueprint for proteins in the cells, the team predicted which unique proteins would 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 the patients’ immune cells can learn what they look like and detect the cancer.
The eight participants each received their personalized vaccine approximately four months after surgery, after which the team collected safety data. The authors experienced only mild side effects, such as fatigue and flu-like symptoms. The team also collected blood samples at various points during the trial, up to a median of four years after vaccination, to examine the T cell responses of patients.
“What is really striking is the durability of the reactions,” said dr. Patrick Ott, a medical oncologist from the Dana-Farber Cancer Institute, Harvard Medical School and Broad Institute, said. “You see persistent reactions in all treated patients a few years ago,” he said. In addition to being long-lived, the responses diversified over time, meaning that T cells learned to recognize neo-antigens not found in the original vaccines.
At the end of the four-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 beginning, we considered vaccines to be a very important adjunctive therapy that can be used in combination with other powerful drugs,” Wu said. In other words, no one expected that the vaccines alone would completely eliminate the patients’ cancer. And because several patients received treatment during the trial, the team was able to see if the vaccine enhanced or undermined these therapies.
Two of the patients who received additional treatment stood out in this regard. In both cases, the cancer spread to their lungs and they were given drugs called ‘checkpoint blockers’, which essentially snatch the brakes of T cells and help boost their activity. With both the vaccine and checkpoint blockages in their systems, both patients’ detectable cancers were quickly eliminated.
“It’s quite unusual to see a complete response just after the initial treatment period … which was the case with both patients,” Ott said. It is an early sign that the vaccine interacts with the control points, which increases the effect of the drugs.
Next steps
In general, only a fraction of melanoma patients benefit from drug barriers, says Dr. Pawel Kalinski, director of cancer vaccine and dendritic cell therapies at the Roswell Park Comprehensive Cancer Center in Buffalo, New York, who was not involved in the study. Other studies have also shown that cancer vaccines can increase the effectiveness of such drugs, and the new clinical trial contributes to the evidence, he said in an email.
That said, “in this small number of patients, [it’s] difficult to draw significant 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. email said., “we think” that the vaccines increase the effect of these drugs and that such findings should remain in larger clinical trials, Brody said.
Theoretically, vaccines could be given to patients to replenish their immune systems and drive T cells to the site of cancer; then drug would come in from the checkpoint for the murder, Ott said. Although it is not known why some patients do not respond to blockages alone, it appears that the drugs work best when T cells are already at the tumor site, Nature News reported; so vaccines can help set up the medicine for success. Vaccines and checkpoint blockers can also be linked to various aids – substances that elicit a strong immune response – and substances that support T survival, Kalinski said.
But, of course, many trials will have to take place before the future becomes a reality.
“The data presented in the current article is certainly very challenging, but addresses relatively few patients whose tumors have been completely cut,” Kalinski said. Future trials will require a control group – to see how patients undergoing surgery plus the vaccine fare, compared to those undergoing surgery alone, he said. In addition, scientists will need to determine which T-cell responses are associated with long-term positive outcomes, he added.
In addition, to be practical in medical care, the vaccines need to be produced faster than in this study, Wu noted. During the trial, vaccine production lasted between 12 and 20 weeks; in the future, this process could be streamlined to take just four to five weeks, she said.
Originally published on Live Science.