A cancer vaccine is one of the holy grails of modern medical research, but finding a way to stimulate the immune system to specifically target and kill cancer cells has proven to be a difficult task. Now two recent clinical trials that have produced encouraging results in patients with skin cancer are are providing hope for the development of personalized cancer vaccines tailored to individual patient's tumors.
Both studies focus on neoantigens, which are mutated molecules found only on the surface of cancer cells. Neoantigens prove to be ideal targets for immunotherapy as they are not present on healthy cells. A vaccine's challenge is to train the body's immune cells, known as T cells, to hunt and kill only those specific tumor cells that hold the target neoantigens.
In the first trial, at Boston's Dana-Farber Cancer Institute, samples of tumors were taken from six patients with melanoma. The patients were identified as having a high risk for recurrence after first having their tumors removed by surgery. For each individual patient the researchers identified up to 20 neoantigens specific to a subject's tumor.
Computer algorithms were then utilized to help the researchers select which specific neoantigens would best stimulate the body's T cells. Those neoantigens were then synthesized, mixed with an adjuvant to stimulate immune response, and injected into the individual patients.
Four out of the six patients in this first trial displayed no recurrence of their cancer 25 months after vaccination. The other two patients did have a recurrence of cancer, although in those cases the cancer had already spread into their lungs. After a secondary treatment with the drug pembrolizumab, they also entered complete remission.
The second trial, by Biopharmaceutical New Technologies (BioNTech) in Germany, used a similar strategy that targeted neoantigens in 13 patients with melanoma. These vaccines targeted up to 10 specific neoantigens in each individual patient, and after 12 to 23 months eight subjects were cancer-free.
The vaccines in both studies successfully stimulated both kinds of cancer-killing T cells: the CD8+ cells and their CD4+ helper cells. The studies also found that the T cells were able to specifically target a patient's tumor.
It's still early stages in research terms, but these results are incredibly promising. With more, and broader, clinical trials set for the near future, it is yet to be seen how effective these kinds of personalized vaccines are across a wide range of different cancers. A larger clinical trial that also targets bladder and lung cancers is currently underway.
One of the big challenges to overcome, should this form of personalized treatment prove broadly successful, is the cost and time in developing these customized vaccines. Current estimates claim a single patient's neoantigen vaccine costs up to $US60,000 to produce. In tandem with other new drug innovations, some patients could be paying several hundred thousand dollars for these treatments should they reach the market.
The time it takes to produce an individual vaccine is also a concern when considering how this treatment could be rolled out on a mass scale. It took several months to produce the vaccines in both studies, but the researchers are confident this time frame could be reduced to six weeks or less. However, this is still a significant amount of time if the process was to be rolled out on a large scale.
Pragmatic challenges aside though, these neoantigen vaccines could pave the way for an exciting new form of personalized cancer treatment. One that allows for specific tumors to be targeted by the immune system through customized vaccines.
Source: Dana-Farber Cancer Institute
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