A personalized mRNA cancer-treatment vaccination strategy is being developed by a team of researchers from Memorial Sloan Kettering Cancer Centre (MSKCC) to target pancreatic ductal adenocarcinoma (PDAC), one of the most common pancreatic cancer.
The study, published in Nature on May 10, is intended to facilitate the immune system's recognition of certain neoantigens — an important protein that can help the body build an immune response — in patients' pancreatic cancer cells.
Despite contemporary medicines, only 12% of PDAC patients will still be alive five years following therapy. The treatment of many tumor types has been revolutionized by immunotherapies, medications that aid the body's immune system in attacking tumors.
But in PDAC, they have so far shown to be useless. It is unclear if pancreatic cancer cells develop neoantigens, proteins the immune system can use to its advantage.
The team submitted tumor samples from 19 patients who underwent surgery to remove PDAC to collaborators at BioNTech, the business that created one of the COVID-19 mRNA vaccines. To identify potential immune-response-inducing proteins, BioNTech performed gene sequencing on the tumors.
They then utilized that data to design an individual mRNA vaccination for every patient. Each vaccination targeted up to 20 neoantigens. For 18 of the 19 trial participants, customized vaccinations were successfully developed. It took an average of nine weeks from the operation to the delivery of the first dose of the vaccine. Before immunization, atezolizumab, an immunotherapy drug, was given to all patients.
The vaccine was subsequently administered over some time in nine doses. Participants in the research began receiving regular PDAC treatment after the first eight doses, and a ninth booster dosage was given after that.
The immunizations stimulated potent immune cells called T cells in half of these patients, allowing them to recognize the patient's particular pancreatic cancer. In collaboration with Benjamin Greenbaum's group at MSKCC, the research team created a unique computational method to monitor the T cells produced following immunization.
What did the findings reveal?
Their investigation revealed that no T cells were capable of recognizing the neoantigens in the blood prior to immunization. Half of the eight individuals with robust immune responses had T cells directed towards several vaccination neoantigens. The cancer had not reappeared in patients with a significant T-cell response to the vaccination by a year and a half following therapy.
However, those whose immune systems did not respond to the vaccination experienced a recurrence of cancer within an average of just over a year. T cells generated by the vaccination seemed to completely eradicate a tiny tumor that had migrated to the liver in one patient with a high reaction.
These findings imply that the pancreatic tumors were controlled by the T cells that the vaccinations stimulated.
To fully understand why just 50% of recipients of personalized vaccinations experienced a robust immune response, more research is required. According to the researchers, a more extensive clinical study for the vaccine will be started.
"It's exciting to see that a personalized vaccine could enlist the immune system to fight pancreatic cancer — which urgently needs better treatments," concludes Vinod Balachandran of MSKCC. "It's also motivating as we may be able to use such personalized vaccines to treat other deadly cancers."
- Nature. Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer
- National Center for Biotechnology Information. Pancreatic ductal adenocarcinoma: Treatment hurdles, tumor microenvironment and immunotherapy