mRNA vaccines increasingly show their potential to transform medicine
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mRNA vaccines against covid-19 appear to have an unexpected advantage: extending the lives of people treated for cancer by enhancing the effectiveness of immunotherapy.
An analysis of records from nearly 1,000 people treated for advanced skin and lung cancers shows that those who received an mRNA covid-19 vaccine within 100 days of starting drugs called immune checkpoint inhibitors lived nearly twice as long as people who were not vaccinated within that time frame. The results will now be confirmed by a clinical trial which should start before the end of the year.
“The results are simply remarkable,” says Elias Sayour of the University of Florida, who believes it will one day be possible to create mRNA vaccines that optimize this response. “Could we create a boilerplate in the form of an mRNA vaccine that would awaken the immune response in everyone with cancer? he said. “You can imagine what the potential of that is.”
In the meantime, should people who have just started taking checkpoint inhibitors get the covid-19 vaccine to boost their treatment success? “I don’t like to make clinical recommendations unless things are proven,” says Sayour. “When you try to use the immune system to fight cancer, there are also risks.” People should continue to follow existing vaccine guidelines, he says.
This discovery is because our immune system kills many cancers long before they become a problem. But some tumors develop the ability to block this response. They do this by taking advantage of immune cell “off switches” called T cells, which kill cancer cells. For example, a common off switch is a protein called PD-1, which protrudes from the surface of these T cells.
PD-1 is turned off when it binds to a protein called PD-L1, found on the surface of some cells. This is a safety mechanism by which cells can effectively say, “stop attacking me, I’m friendly.”
Many cancers hijack this by producing lots of PD-L1. Checkpoint inhibitors work by preventing the activation of PD-1 or other off switches. They have significantly improved survival rates for lung cancer and melanoma, among others, and won a Nobel Prize for their creators in 2018.
But the effectiveness of checkpoint inhibitors varies widely. If a person’s immune system hasn’t responded to a tumor by sending T cells to attack it, drugs can’t help much.
So combining checkpoint inhibitors with vaccines that stimulate the immune system to attack tumors may be much more effective than either approach alone. Cancer vaccines are typically designed to trigger a response to mutated proteins on cancer cells and are often personalized to individuals. “We’re trying to understand what’s unique about their tumor,” says Sayour. “It’s time consuming, expensive and complex.”
During cancer vaccine trials, his team realized that the nonspecific mRNA vaccines they used as controls also appeared to have a large effect. “It was an absolute surprise,” says Sayour.
In July of this year, Sayour and colleagues reported how mRNA vaccines boost anti-tumor responses, even though they do not target a cancer protein, based on studies in mice. Vaccines trigger an innate immune response that acts like a siren, he says, waking up the immune system and causing T cells to migrate from tumors to lymph nodes, where they stimulate other cells to launch a targeted attack.
If this is a general property of mRNA vaccines, the team realized, it should also be true for those against covid-19. Now, Sayour and colleagues examined the records of people treated at the University of Texas MD Anderson Cancer Center.
Of the 884 people with advanced lung cancer who received checkpoint inhibitors, 180 received an mRNA vaccination against covid-19 100 days after starting treatment. They had a survival time of around 37 months, compared to 20 months for those who were not vaccinated.
In addition, 210 people had melanomas that had started to spread to other parts of the body, 43 of whom were vaccinated within 100 days of starting to take checkpoint inhibitors. They had a survival time of around 30 to 40 months, compared to 27 months for those who had not been vaccinated during this period – and because some vaccinated people were still alive at the time of the analysis, their survival time could be even longer. The team presented the results today at a meeting of the European Society for Medical Oncology Congress in Berlin, Germany.
Some cases of tumors shrank after people received the mRNA covid-19 vaccines, suggesting that they may, on occasion, have anti-tumor effects even if people do not take checkpoint inhibitors. “It’s certainly possible, but more research would be needed to answer this,” says Sayour.
The United States recently announced significant reductions in funding for the development of mRNA vaccines, despite their immense benefits during the pandemic and their enormous potential for developing treatments beyond vaccines.
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