Could RNA errors prove to be a prevention for cancer? Scientist Stephen Albert Johnston and his team at Arizona State University’s Biodesign Institute (ASU) think maybe it could. After a decade’s research, he and his team believe they might have found the answer to a universal vaccine to prevent cancer.
Johnson says that the mindset is simple: treat cancer just like an infectious disease. So, when his team looked deep within tumors, they found 200,000 cancer neoantigens — the components of cancer vaccines — that had been missed by other scientists. They also found that enough of these neoantigens occurred repeatedly in different tumors that it might be possible to make one vaccine for all tumors.
The source of these neoantigens? RNA errors of tumors, which involve changing the reading of the coding for proteins. Johnston said in cancer cells, levels of information transfer from DNA to RNA to protein become more error-prone.
“We proposed that these mistakes made in cancer cells may also be the source to make a cancer vaccine,” he said.
The erroneously produced proteins are called frameshift peptides. To try to ID these frameshift and slicing mutations, the ASU team designed an array of possible frameshift peptides and were able to determine those that are unique to an individual or shared by specific tumor types. From there, they could then pick vaccine candidates. In studies on mice, the vaccines showed promise in fending off tumors.
The ASU study examined mutations in more than 50 cancer cell lines, and 85 tissue samples from Mayo Clinic Arizona cancer patients, as well as the blood from patients from five different late-stage cancer types: lung, breast, brain, gastric and pancreatic cancers.
“Personal cancer vaccines are complicated and expensive,” said Johnston. “Also, only about 40 percent of tumors have enough mutations in the DNA to make a vaccine from. We discovered that even ‘cold tumors’ at the DNA level make lots of mistakes at the RNA level. And the mistakes we focus on are frameshift peptides which are much more immunogenic than the point mutations used in personal cancer vaccines. Most importantly, we can make off-the shelf vaccines for therapeutic or even preventative vaccines which will be much less expensive.”
All of the frameshift alterations, identification and screening experiments allowed them to choose the top vaccine candidates. These were tested in several mouse studies in a variety of cancer prevention and therapy challenges.
The researchers found that these vaccines could all significantly delay or even prevent tumor growth. However, the most important discovery from the mouse vaccine challenges were that pooling multiple frameshift peptides produced a significant additive increase in delaying tumor growth, and made for a more effective vaccine.
Johnston said they have the technology to make the human vaccine right now, but even optimistically it would be five to 10 years before human use.
“This is probably the only approach to a broadly preventative cancer vaccine, so we feel we have to try it,” said Johnston. “The implications of success would be quite large.”
The findings appeared in the journal Nature Scientific Reports.