A mRNA-based cancer vaccine has shown impressive results in a small trial in patients with pancreatic cancer, showing that the vaccine can stimulate a long-term immune response that reduces the risk of cancer recurrence after surgery.
New results from the phase I clinical trial testing mRNA vaccine autogene cevumeran were published in the journal Nature. They show that the mRNA vaccines, in combination with another type of immunotherapy called an immune checkpoint inhibitor stimulated an immune response against proteins found on the tumor. These immune cells were detected in trial patients up to four years after treatment, showing that although mRNA vaccines themselves are short-lived in the body, anti-tumor immune cells stimulated by them can last for years.
“The latest data from the phase 1 trial are encouraging,” said Vinod Balachandran, MD, surgeon-scientist from Memorial Sloan Kettering Cancer Center in New York and principal investigator of the trial. “They suggest this investigational therapeutic mRNA vaccine can mobilize anti-tumor T cells that may recognize pancreatic cancers as foreign, potentially years after vaccination,” said Balachandran, also senior author of the new publication.
Cancer vaccines do not work like vaccines for infectious diseases such as Covid-19 or measles. These vaccines are generally given to people preventively to reduce the chance of them getting sick, or seriously ill from viruses, bacteria or other microorganisms. Cancer vaccines are given to people who already have cancer and prompt the immune system to attack the tumor.
Much like there are different formulations of mRNA vaccines for Covid-19, adapted to different virus variants, the mRNA vaccines used in the trial were personalized for each patient. Using genetic sequencing information, researchers designed a mRNA vaccine to stimulate the immune system against proteins called neoantigens specifically present on each patient’s tumor. An earlier report on the study showed that the vaccines had no major side-effects and around half of patients on the trial had a detectable immune response.
“For patients with pancreatic cancer, our latest results continue to support the approach of using personalized mRNA vaccines to target neoantigens in each patient’s tumor,” said Balachandran. “If you can do this in pancreas cancer, theoretically you may be able to develop therapeutic vaccines for other cancer types.”
Although the results should be interpreted with caution as the trial only involved a small number of patients, of which only half responded, the results are still exciting as pancreatic cancer has a dismal survival rate, with only 13% of patients alive 5-years or more after diagnosis. Regular treatments such as surgery and chemotherapy are of limited benefit and most patients experience relapse of their disease. Of the 8 patients that responded initially to the mRNA vaccine, 6 remain cancer free at the time of study follow up.
mRNA-based cancer vaccines were already in development several years before the Covid-19 pandemic brought the technology to worldwide attention. As well as pancreatic cancer, they are in trials for several different types of cancer, including skin cancer, kidney cancer, brain cancer and breast cancer.
The initial results of the mRNA vaccine in pancreatic cancer were promising enough that a much larger phase 2 trial of 260 patients is already underway. Patients will be randomized into two groups, patients in one will receive surgery followed by conventional chemotherapy treatment and the other will receive surgery, a personalized mRNA vaccine and also an immune checkpoint inhibitor drug to aid the immune response after the vaccine. The study is expected to finish in 2029, but interim results should be available at several points before that as researchers track the preliminary results of the trial.
