An experimental approach to treating pancreatic cancer with the messenger RNA (mRNA)-based therapeutic cancer vaccine autogene cevumeran continues to show potential to stimulate an immune response that may reduce the risk of the disease returning after surgery in a small patient group. New results from the phase 1 clinical trial, now published in the journal Nature, show that the therapeutic cancer vaccine activated tumor-specific immune cells that persisted in the body up to nearly four years after treatment in some patients. In addition, patients with a vaccine-induced immune response had a reduced risk of the cancer coming back at a three-year follow-up compared with patients whose immune systems did not respond.
“The latest data from the phase 1 trial are encouraging,” says Vinod Balachandran, MD, principal investigator of the trial and senior author of the new publication. “They suggest this investigational therapeutic mRNA vaccine can mobilize anti-tumor T cells that may recognize pancreatic cancers as foreign, potentially years after vaccination.”
Dr. Balachandran is a pancreatic cancer surgeon-scientist in the Human Oncology and Pathogenesis Program and Director of The Olayan Center for Cancer Vaccines (OCCV) at Memorial Sloan Kettering Cancer Center (MSK). The OCCV is a research hub that spans the full spectrum of basic discovery to clinical application of cancer vaccines.
The phase 1 study tested autogene cevumeran (BNT122, RO7198457), a therapeutic mRNA cancer vaccine developed and researched through a collaboration between BioNTech, an immunotherapy company, and Genentech, a member of the Roche Group.
The therapeutic mRNA cancer vaccine was personalized for each of the 16 participants in the trial based on the mutational profile of each patient’s tumor. As reported in 2023 in Nature, the vaccine was safe with no serious side effects and stimulated an immune response in half of patients.
Therapeutic cancer vaccines such as autogene cevumeran are designed to treat — not prevent — cancer. By delivering proteins found exclusively in cancer (called neoantigens), these vaccines aim to train the immune system to recognize cancer cells as foreign.
Therapeutic cancer vaccines that can stimulate a robust, long-lived immune response with clinical impact have remained largely elusive. But recent research and technological developments in mRNA technology are changing the field. This approach is primarily aimed at the early stages of cancer, where the cancer has not yet spread and tumors can be surgically removed, to help delay or prevent recurrence.
In these findings from the phase 1 trial, the researchers could detect vaccine-stimulated T cells at substantial frequencies up to nearly four years after treatment. The team was able to track the vaccine-induced T cells with the help of computational biologist Benjamin Greenbaum, PhD.
The vaccine-stimulated T cells retained their anti-cancer activity, even after patients received chemotherapy following initial doses of the vaccine. Researchers had wondered whether chemotherapy might somehow diminish the effects of the vaccine. It did not seem to in this small, early study.
“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,” Dr. Balachandran says. “If you can do this in pancreas cancer, theoretically you may be able to develop therapeutic vaccines for other cancer types.”
Pancreatic cancer is one of the deadliest cancers, even for patients whose tumors are removed with surgery. Only about 13% of patients are alive five years after diagnosis, according to the American Cancer Society. Chemotherapy, radiation, targeted therapy, and current immunotherapies are also largely ineffective against pancreatic cancer, so new therapies are urgently needed for patients who face this disease.
Dr. Balachandran’s team in the OCCV aims to innovate next-generation cancer vaccines, with initial goals to expand vaccine use in pancreatic and other cancers lacking effective treatments.
The investigator-initiated, single-center phase 1 clinical trial involved studying 16 MSK patients who received the investigational therapeutic cancer vaccine autogene cevumeran, along with an immunotherapy drug called atezolizumab and a chemotherapy regimen called mFOLFIRINOX. Early immunological and clinical results from the trial published in Nature in 2023 showed this treatment was generally well tolerated and stimulated an immune response that correlated with delayed recurrence at a 1.5-year median follow-up compared with non-responders.