Researchers at the University of Connecticut have found a new way to identify protein mutations in cancer cells. The novel method is being used to develop precision medical vaccines to treat patients with ovarian cancer. This has the potential to dramatically change how the medical community treats cancer. This research will serve as the basis for the first ever genomics-driven precision medicine clinical trial in immunotherapy of ovarian cancer, and will begin at UConn Health this fall. The results appear in the Journal of Experimental Medicine.
Once it is approved by the FDA the research team will sequence DNA from the tumours of 15 to 20 women with ovarian cancer, and use that information to make an individualised vaccine for each woman.
The researchers focused their clinical trial on patients with ovarian cancer because the disease usually responds well to surgery and chemotherapy in the short term, but often returns lethally within a year or two. That gives researchers the perfect window to prepare and administer the new therapeutic vaccines, and also means they may be able to tell within two years or so whether the vaccine made a difference. If the precision medicine vaccines prove to be safe and feasible, they’ll design a Phase II trial to test its clinical effectiveness by determining whether they prolong patients’ lives.
In order for the immune system to attack cancers, it first has to recognize them. Every cell in the body has a sequence of proteins on its exterior that acts like an ID card or secret handshake, confirming that it’s one of the good guys. These protein sequences, called epitopes, are what the immune system ‘sees’ when it looks at a cell. Cancerous cells have epitopes, too. Since cancer cells originate from the body itself, their epitopes are very similar to those of healthy cells, and the immune system doesn’t recognize them as bad actors that must be destroyed.
But just as even the best spy occasionally slips up on the details, cancer cell epitopes have tiny differences or mistakes that could give them away, if only the immune system knew what to look for.
The researchers want to break the immune system’s ignorance. For example, there could be 1,000 subtle changes in the cancer cell epitopes, but only 10 are ‘real,’ meaning significant to the immune system. To find the real, important differences the team took DNA sequences from skin tumours in mice and compared them with DNA from the mice’s healthy tissue.
Previous studies had done this but looked at how strongly the immune system cells bound to the cancer’s epitopes. This works when making vaccines against viruses, but not for cancers. Instead the team came up with a novel measure, they looked at how different the cancer epitopes were from the mice’s normal epitopes. And it worked. When mice were inoculated with vaccines made of the cancer epitopes differing the most from normal tissue, they were very resistant to skin cancer.
Theoretically, this approach could work for other cancers, although the research has yet to be done.
Researchers in cancer biology, immunology, and computational bioinformatics worked together to discover these connections. The researchers have applied for two patents for their new technique, and a Connecticut start-up company, Accuragen Inc., has obtained an option to license the patents.
Creating a safe, effective cancer vaccine is one of the major long-term goals of precision medicine. Using a different approach than the one described in this paper, the team’s research has already created a vaccine against kidney cancer, which is in clinical use and commercially available in Russia.
It is known that patients have genetic sequences that make them better candidates for some drugs than others. And researchers can figure that out much more easily now than five years ago. The novelty of the current study’s approach is that it results in a drug specifically designed for a single person. If the approach proves safe and effective, it would be the ultimate in individualized precision medicine.
Source: University of Connecticut
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