mRNA vaccines are increasingly showing their potential to transform medicine
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mRNA covid-19 vaccines appear to have an unexpected benefit: extending the lives of people being treated for cancer by enhancing the effectiveness of immunotherapy.
An analysis of records from nearly 1,000 people being treated for advanced skin and lung cancers shows that those given the mRNA Covid-19 vaccine within 100 days of starting drugs called immune checkpoint inhibitors lived nearly twice as long as people who did not get vaccinated during this time. The results will now be confirmed in a clinical trial scheduled to begin before the end of the year.
“The results are amazing,” he says. Elias Sayur at the University of Florida, who believes it will one day be possible to create mRNA vaccines that improve this response. “Can we create a master switch in the form of an mRNA vaccine that awakens the immune response in every person with cancer?” He says. “You can imagine what the potential is.”
In the meantime, should people who are just starting to take checkpoint inhibitors get vaccinated against COVID-19 to boost the success of their treatment? “I don’t like to make clinical recommendations unless things are proven,” says Sior. “When you try to use the immune system to fight cancer, there are risks, too.” He says people should continue to follow current vaccine guidelines.
The background to this finding is that our immune system kills many cancers long before they become a problem. But some tumors develop the ability to turn off this response. They do this by taking advantage of “kill switches” found in immune cells called T cells, which kill cancer cells. For example, one 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, which is found on the surface of some cells. This is the safety mechanism by which cells can effectively say: “Stop attacking me, I’m friendly.”
Many cancers hijack this by producing too much PD-L1. Checkpoint inhibitors work by turning off PD-1 or other off switches. They have dramatically improved survival rates for lung cancers and melanomas, among other diseases, and won a Nobel Prize for their creators in 2018.
But the effectiveness of checkpoint inhibitors varies widely. If a person’s immune system does not respond to the tumor by sending T cells to attack it, medications will not help much.
So combining checkpoint inhibitors with vaccines that stimulate the immune system to attack tumors could be much more effective than either approach alone. Cancer vaccines are usually designed to stimulate a response to mutant proteins found in cancer cells, and are often tailored to individuals. “We’re trying to figure out what’s special about their tumor,” Sayor says. “It takes a lot of time, cost and complexity.”
During cancer vaccine trials, his team realized that the nonspecific mRNA vaccines they were using as controls also seemed to have a significant effect. “That was an absolute surprise,” Sayur says.
In July this year, Sayor and colleagues reported how mRNA vaccines enhance anti-tumor responses, even if they do not target a cancer protein. According to studies conducted on mice. He says vaccines trigger an innate immune response that acts like a siren, stimulating the immune system and making T cells migrate from tumors to lymph nodes, where they stimulate other cells to launch a targeted attack.
The team realized that if this was a general property of mRNA vaccines, it should also be true for COVID-19 vaccines. Now, Sayor and his colleagues have looked at records of people treated at the University of Texas MD Anderson Cancer Center.
Of the 884 people with advanced lung cancer who were given checkpoint inhibitors, 180 got the mRNA Covid-19 vaccine 100 days after starting the drugs. They had a survival time of about 37 months, compared to 20 months for those who were not vaccinated.
In addition, 210 people developed melanomas that began to spread to other parts of the body, and 43 of them were vaccinated within 100 days of starting checkpoint inhibitors. They had a survival time of about 30 to 40 months, compared to 27 months for those who were not vaccinated during this time – and since some of the vaccinated people were still alive when the analysis was done, their survival time may have been even higher. The team presented the findings at the European Society of Medical Oncology meeting in Berlin, Germany, today.
There have already been some Status reports Of tumors shrinking after people got mRNA covid-19 vaccines, suggesting they could, sometimes, have anti-tumor effects even if people didn’t take checkpoint inhibitors. “It’s certainly possible, but more research will be necessary to answer that,” Sayor says.
The United States recently announced significant cuts in funding for the development of mRNA vaccines, despite their enormous benefits during the pandemic and the enormous potential for developing treatments beyond vaccines.
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