Messenger RNA (mRNA) vaccines – famous for preventing symptomatic infection of COVID-19—are starting to show some promise against pancreatic cancer.

A research team led by Dr Vinod Balachandran from Memorial Sloan Kettering Cancer Center (MSK) in New York has developed personalised mRNA vaccines that could train the immune system to kill pancreatic cancer cells. The jab uses the same mRNA theory that is present in COVID vaccines. The hope is that the mRNA vaccine will stimulate the production of immune cells, named T cells, that recognise pancreatic cancer cells. Researchers believe that this could reduce the risk of cancer returning once the primary tumour has been removed by surgery. 

In the phase I trial, MSK doctors extracted patients’ tumours and shipped samples of them to Germany. There, scientists that made a highly successful COVID vaccine analysed the genetic makeup of specific proteins on the surface of the cancer cells. Using that genetic data, scientists produced personalised mRNA vaccines designed to teach each patient’s immune system to attack the tumours. These vaccines instructed patients’ cells to make some of the same proteins found in their excised tumours, potentially provoking an immune response against pancreatic cancer cells.

The results published in Nature on 10 May 2023 suggest that personalised pancreatic cancer vaccines cause an effective and lasting immune response, potentially delaying its relapse. Customised vaccines were successfully created for 16 participants (patients with pancreatic ductal adenocarcinoma surgically resected). The process, from surgery to delivery of the first dose of the vaccine, took approximately nine weeks.

In half of these patients, the vaccines activated powerful immune cells, called T cells, that could recognise pancreatic cancer specific to the patient. A year and a half after treatment, the cancer had not returned in people with a strong T-cell response to the vaccine. In contrast, cancer recurred within an average of just over a year amongst those whose immune systems did not respond to the vaccine. In one patient with a particularly strong response, T cells produced by the vaccine even appeared to eliminate a small tumour that had spread to the liver. These results suggest that the T cells activated by the vaccines kept the pancreatic cancers in check. Out of the 16 patients with immune responses, 8 did not relapse at a median follow-up of almost a year and a half, which is quite extraordinary given the lack of effective drugs outside of chemotherapy in that setting.  

More work is needed to understand why half the trial participants did not have a robust immune response to their personalised vaccines. Following these promising results, the next step is to launch a larger, randomized clinical trial involving patients at multiple sites in various countries. MSK expects to begin enrolling patients in the trial this summer (2023).

References

Rojas LA, et al. Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer.  Nature. 2023 May 10:1-7. doi: 10.1038/s41586-023-06063-y.