mRNA vaccines increasingly demonstrate their potential to transform medicine
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Covid-19 mRNA vaccine appear to have an unexpected benefit: extending the lives of people being treated for cancer by increasing the effectiveness of immunotherapy.
An analysis of records from nearly 1,000 people being treated for advanced skin and lung cancer shows that those given 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 during that time. The results will now be confirmed in clinical trials due to begin before the end of the year.
“The results are simply wonderful,” says Elias Sayur from the University of Florida, who believes it may one day be possible to create mRNA vaccines that optimize this response. “Can we create a master key in the form of an mRNA vaccine that triggers an immune response in all cancer patients?” he says. “You can imagine the potential in this.”
Meanwhile, should people who have just started taking checkpoint inhibitors get vaccinated against Covid-19 to improve treatment success? “I don’t like to make clinical recommendations until something is proven,” Sayur says. “When you try to use the immune system to fight cancer, there are also risks.” People should continue to follow existing vaccination recommendations, he said.
This discovery is based on our immune system kills many types of cancer long before they become a problem. But some tumors develop the ability to turn off this response. They do this by using “switches” of immune cells called T cells that kill cancer cells. For example, one common switch is a protein called PD-1, which protrudes from the surface of these T cells.
PD-1 flips to the off position when it binds to the PD-L1 protein 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 disrupt this function by producing large amounts of PD-L1. Checkpoint inhibitors work by stopping PD-1 or other switches from being pressed. They have survival rates have improved significantly for lung cancer and melanoma, among others, and received the 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 a tumor by sending T cells to attack it, drugs I can't help much.
Thus, 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 usually designed to trigger a response to mutant proteins found in cancer cells. often personalized to private individuals. “We're trying to figure out what's unique about their tumor,” Sayur says. “It takes a lot of time, cost and complexity.”
During testing Cancer vaccines, his team realized that the nonspecific mRNA vaccines they used as a control also seemed to have a large effect. “It was an absolute surprise,” says Sayur.
This July, Sayur and colleagues reported how mRNA vaccines enhance antitumor responses even when they don't target a cancer protein. based on mouse studies. The vaccines trigger an innate immune response that acts like a siren, awakening the immune system and causing T cells to migrate from tumors to lymph nodes, where they stimulate other cells to launch a targeted attack, he said.
The team realized that if this is a general property of mRNA vaccines, then it should also be true for Covid-19 vaccines. Now Sayur and his colleagues studied the records of people treated at the M.D. Cancer Center. Anderson at the University of Texas.
Of 884 people with advanced lung cancer treated with checkpoint inhibitors, 180 received the Covid-19 mRNA vaccine 100 days after starting the drugs. Their survival time was about 37 months, compared with 20 months for those who were not vaccinated.
In addition, 210 people had melanoma that had started to spread to other parts of the body, 43 of whom were vaccinated within 100 days of starting checkpoint inhibitors. Their survival time was 30 to 40 months, compared with 27 months for those who were not vaccinated during that time – and since some of the vaccinated people were still alive at the time of the analysis, their survival time may be even longer. The team presented the results today at the European Society of Medical Oncology Congress meeting in Berlin, Germany.
Previously there were some case reports tumors decreased after people received mRNA Covid-19 vaccines, suggesting they may sometimes have antitumor effects even if people don't take checkpoint inhibitors. “This is certainly possible, but more research will be needed to answer this question,” Sayur says.
The US recently announced big funding cuts for the development of mRNA vaccines, despite their huge benefits during a pandemic and huge potential for developing treatments in addition to vaccines.
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