An early-stage mRNA vaccine has the potential to induce an immune response against pancreatic cancer cells, reducing the risk of the tumor returning after surgery.
About Pancreatic Cancer
Pancreatic cancer is known for having a high mortality rate, even when caught early. Because the disease is challenging to detect in early stages and often spreads, surgery by itself is rarely curative. Currently available including chemotherapy, radiation, targeted therapy, and immunotherapy have had little impact on improving long term survival – developing new therapies is crucial.
What are mRNA Vaccines and How Can They be Used to Treat Pancreatic Cancer?
One proposed strategy to improve long term survival involves harnessing the power of the immune system. The messenger RNA (mRNA)-based therapeutic cancer vaccine autogene cevumeran has the potential to enable the immune system to recognize and attack pancreatic cancer cells, reduce the risk of the cancer returning after surgery. The vaccine uses mRNA, genetic code, to teach T cells to make a protein. This protein triggers an immune response when the T cells recognize neoantigens, proteins found primarily in a patient’s pancreatic cancer. The ultimate goal of this mRNA vaccine is to train the body to protect itself against cancer cells.
New results from a phase 1 clinical trial conducted by Dr. Vinlod Balachandran at Memorial Sloan Kettering Cancer Center (MSKCC) indicated that the vaccine autogene cevumeran activated immune cells in half of patients treated with the vaccine. In some patients, these activated immune cells persisted in the body for up to three years. This vaccine-induced immune response correlated with a reduced risk of the cancer returning.
Results
Initial results from the phase 1 trial at MSKCC indicated that the vaccine was well tolerated and activated immune cells in half of the treated patients for up to three years.
The investigator-initiated, single-center trial involved studying 16 patients who received the mRNA vaccine in addition to an immunotherapy drug called atezolizumab and a chemotherapy regimen called mFOLFIRINOX. Patient outcomes were assessed in follow-ups up to three years after treatment:
- The investigational cancer vaccine effectively induced T cells specific to vaccine-encoded neoantigens in eight patients. During the follow-up window, six of the eight patients remained tumor-free, and two patients relapsed. Blood and tissue samples from these patients before and after receiving vaccines indicated that 98% of the T cells activated by the vaccines were not present before vaccination. Additionally, the response appeared durable, as >80% of the vaccine-induced T cells persisted 2-3 years after treatment.
- Eight patients did not have an immune response to the vaccine. Seven of those eight patients relapsed during the follow-up window.
Researchers will continue to investigate whether the vaccines delayed cancer recurrence in patients with successfully activated T cells.
Phase 2
A phase 2 clinical trial that began in July 2023 will compare the effectiveness of the mRNA vaccine to standard treatment. The trial will be conducted at MSKCC and other sites around the world and will enroll 260 patients.
The trial contains two groups of patients. The first is the control group that will receive standard pancreatic cancer treatment: surgery followed by chemotherapy.
The second group will receive the experimental mRNA based treatment: surgery followed by the mRNA vaccine, an immunotherapy drug called a checkpoint inhibitor, and chemotherapy. After a patient has a pancreatic tumor surgically removed, the tumor’s genes will be sequenced to identify mutations likely to contain high numbers of neoantigens, and mRNA vaccines will be custom-made based on these sequences. Vaccines will be given in two phases. The first doses will prime the immune system, and the later doses will provide a boost. The vaccine will be infused into the bloodstream and cause dendritic cells, a type of immune cell, to make neoantigen proteins. Then, the dendritic cells will train the rest of the immune system, including T cells, to recognize and attack the tumor cells that express the same proteins. If the T cells can destroy all cells carrying these proteins, the cancer may have a lower chance of returning.
Background on Using mRNA Vaccines to Treat Pancreatic Cancer
The basis for using mRNA vaccines to treat pancreatic cancer lies in preliminary research conducted at MSKCC. Researchers investigated why a small subset of patients successfully survived pancreatic cancer after tumor removal and determined that they contained a large number of immune cells in their tumors. These findings led researchers to believe that something in the tumor cells acted as a signal and alerted T cells. These signals turned out to be neoantigens, proteins caused by genetic mutations that accumulate when tumor cells divide. Most immune systems fail to detect neoantigens. However, the small number of pancreatic cancer survivors contained T cells that could recognize the foreign neoantigens and trigger an immune system attack. T cells with the ability to recognize neoantigens circulated in patients’ blood for up to 12 years after the tumor was removed by surgery.
For more information about enrolling in the mRNA vaccine trial at MSKCC, call the Patient Access Service at 332-266-3739.
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