Tim Radford Scientists claim this week to be on the track of a “universal” cancer vaccine. They have targeted a natural protein that makes tumour cells immortal and therefore lethal. The scientists have isolated part of the protein and used it to trigger immune system cells into killing both mouse and human cancer cells in laboratory dishes. The same protein has also been shown to slow the growth of melanoma, breast and bladder cancers in living laboratory mice. The substance at the heart of the latest twist in the war against cancer is called telomerase. Tumours are cells that will not die – and telomerase is the substance in the cell that prevents them from doing what healthy cells do in time, which is commit suicide. Telomerase is found in all major cancers. The classic cancer treatments, by radiation, surgery or drugs, are uncertain and often wretched for the patient. Researchers have begun to pin their hopes on genetically based vaccines as a new way of stopping cancers, or preventing cancers from returning. Scientists in Britain have just begun to assemble a library of hundreds of genes specific to different kinds of cancers and these could ultimately be the basis for hundreds of unique treatments. But telomerase has presented scientists with a single target. And a United States team based in North Carolina reports in the September issue of Nature Medicine that telomerase could be the basis of a new kind of all-purpose vaccine.
“The thinking has been that because every cancer is different – melanoma, breast, etc – that each cancer has its own specific set of antigens that must be used for a vaccine,” said Eli Gilboa of the Duke University medical centre.
“We are looking for a universal antigen – one antigen to try to treat every cancer patient.” Cancer vaccines work by stimulating the immune system to produce an army of cells that recognise, attack and kill specific targets: in this case, cancer cells. The Duke researchers worked with the Geron Corporation, a leading biotech company. They used RNA – the gene’s instructions for building proteins – to persuade key cells to make and display a certain part of the telomerase protein on their surfaces. These key cells play a powerful role in kicking the immune system into action. The researchers also made vaccines specific to certain tumours and compared them to the telomerase vaccine. The tumour-RNA vaccines set up immune responses that were more efficient at killing the tumours. But the telomerase vaccine set up a response that recognised and killed a much wider variety of cancer cells. It slowed the growth of mela- noma, breast and bladder cancers in mice, and it was effective against sets of mouse cancer cells in the laboratory. No other vaccine produced such a broad response. The research has only been in mice, or cells in a laboratory dish. Human tests are a long way off. Cancer researchers in Britain zeroed in on telomerase last year, when they found a way of switching off this “immortality” enzyme. Doing this would, in effect, tell a tumour to commit suicide. But it is one thing to propose a magic bullet, quite another thing to make it and fire it accurately at the enemy. “Teams all over the world are looking at the development of new thera-peutics with telomerase as the target. But the vast majority are not looking at it as an immune target. It’s a novel approach,” said Lesley Walker of the Cancer Research Campaign. “Telomerase is not switched on in all cancers, so the claim to universal is a bit rich. But we know what they mean.”
And Nick Lemoine of the Imperial Cancer Research Fund saw other difficulties. Telomerase was certainly present in high levels in tumour cells – but it was also present in the stem cells of bone marrow, reproductive organs and perhaps other tissues. Triggering the immune system to search for and destroy telomerase cells could do more harm than good. “The idea that it might be possible to create a universal vaccine for all cancers is appealing, but unlikely to be achieved because there are many different types of cancer,” he said.