A personalized vaccine developed by researchers in the UK and China extended the survival of mice with pancreatic cancer, opening the door to the first treatments to prevent rather than treat one of the most aggressive forms of cancer.
“Pancreatic cancer remains one of the most challenging tumors to treat,” said Yaohe Wang, professor at Queen Mary University of London, explaining that this form of cancer spreads to other organs quickly and often does not show symptoms until it is very advanced.
“Pancreatic cancer has unique molecular genetic changes that suppress anti-tumor immune responses very effectively, so it is unresponsive to new immunotherapy treatments such as immune checkpoint inhibitors that are showing great success in a number of other cancers.”
In collaboration with researchers from Zhengzhou University in China, Wang’s group devised a strategy to immunize people against pancreatic cancer before it develops.
“All cancer vaccines currently in clinical trials are used to treat established tumors,” Wang said. “Our technology aims to create preventative vaccines given before tumor development to at-risk populations to prevent the initial outgrowth of cancer before the disease has a chance to progress and suppress the immune system.”
The challenge here is that there is a big variability between individuals with pancreatic cancers. A vaccine that primes the immune system against a certain cancer antigen might work for some patients but not for others. To circumvent this problem, the researchers designed an approach to immunize against pancreatic cancer before it forms, and tested it in mice.
Using stem cells derived from a sample of the skin of a healthy individual, the scientists introduced genetic modifications that would make the cells become cancerous and transformed them into pancreatic cells. Before injecting them into the mouse, the cells were infected with viruses that enhanced the immune system response and were then killed chemically.
Once in the body, the cells release a large number of cancer antigens that are unique to the individual. The immune system will thus learn to attack any cells presenting these antigens in the future.
This method also addresses the challenge of the huge variability seen within tumor cells in a single individual. “We really need to identify a large number of antigens to target in order to ensure that all tumor cells are eliminated by the immune system. If we only target one or a few, it is likely that many tumor cells will be missed and continue to proliferate,” explained Wang.
The method has so far been tested in mice that were genetically programmed to develop pancreatic cancer. In a study published in Clinical Cancer Research, mice treated with this personalized vaccine saw an extension of their lifespan of up to 51% compared to untreated mice.
Wang estimates it will take between 5 and 7 years until this approach will be ready to get regulatory approval to be tested in humans. The study, however, acts as a proof of concept for a new kind of cancer vaccine. While personalized cancer vaccines are already in clinical development, this approach would be unique in being able to prevent the development of the disease rather than deal with its consequences. The researchers are now looking at funding and partnering opportunities to help turn this discovery into a commercial application.
The publication also noted that determining which people would benefit from this approach remains challenging. However, in recent years, scientists have reported a series of mutations that put certain individuals at a high risk of developing pancreatic cancer, who would be the ideal candidates to benefit from this kind of preventive approach.