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Personalized mRNA Cancer Vaccine Trials Show Extended Survival in Pancreatic Cancer and Melanoma

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A Series of Clinical Trials Reports Long-Term Follow-Up Data on Personalized mRNA Vaccines for Cancer

Pancreatic Cancer Vaccine Trial

Trial Design and Participants

A Phase 1 clinical trial at Memorial Sloan Kettering Cancer Center tested a personalized mRNA vaccine in 16 patients with early-stage, operable pancreatic cancer. The trial was led by Dr. Vinod Balachandran.

After surgical removal of their tumors, patients received a vaccine personalized using genetic material from their own tumor cells. The vaccine was developed in collaboration with BioNTech in Germany. Patients also received an immune checkpoint inhibitor (immunotherapy) followed by standard chemotherapy.

Results and Survival Data

  • Eight of the 16 patients (50%) developed a strong immune response to the vaccine, producing T cells that target tumor cells.
  • At the six-year follow-up mark, seven of the eight patients who generated an immune response (87.5%) were alive. Among the eight patients who did not generate a response, two were alive (25%).
  • Two patients in the responder group experienced a cancer recurrence; one responder died.
  • The median survival for non-responders was reported as 3.4 years.
  • Researchers estimated that the immune cells produced by the vaccine had an average lifespan of approximately 7.7 years, with about 20% expected to last over a decade.

"The trial results imply a strong, lasting immune response can be generated against difficult cancers." — Dr. Vinod Balachandran

Background and Mechanism

Pancreatic cancer has a five-year survival rate of less than 13%. Approximately 20% of cases are operable at the time of diagnosis.

The vaccine is designed to train the immune system to recognize and eliminate lingering cancer cells to prevent recurrence, rather than to shrink existing tumors. The approach was inspired by a 2017 study of long-term pancreatic cancer survivors whose immune systems showed a strong ability to recognize cancer cells. The mRNA technology allows for rapid customization of the vaccine to target specific mutations in each patient's tumor.

Expert Statements

Dr. William Freed-Pastor of Dana-Farber Cancer Institute noted that the finding that patients who mounted an immune response lived longer is significant, but cautioned that other factors could explain both the immune response and the survival.

Dr. Robert Vonderheide of the American Association for Cancer Research noted that a subgroup of pancreatic cancer patients typically survives longer than five years, which is important context for evaluating new therapies. He also stated that earlier mRNA vaccine research for advanced cancer was disappointing, but newer research suggests it may work in less advanced cases.

Patient Case

Vita Sara Blechner, a 67-year-old from Oceanside, New York, was diagnosed with pancreatic cancer in March 2020. She participated in the trial, undergoing surgery followed by the personalized vaccine regimen. She experienced severe side effects from subsequent chemotherapy, which was halted. More than six years after diagnosis, she shows no sign of cancer.

Melanoma Vaccine Trial

Trial Design and Participants

A Phase 2 clinical trial tested a personalized mRNA vaccine (mRNA-4157/V940) in combination with the immunotherapy drug pembrolizumab (Keytruda) for patients with high-risk melanoma.

The trial included 157 patients in the U.S. and Australia who had surgical removal of their tumors. Patients received either the combination therapy (107 patients) or pembrolizumab alone (50 patients).

Results

  • At the five-year follow-up, 68.8% of patients receiving the combination therapy remained cancer-free, compared to 49.1% in the pembrolizumab-only group. This represents a 49% reduction in the risk of recurrence.
  • 92% of combination therapy patients were alive at five years, compared to 71% in the control group.
  • The vaccine reduced the risk of metastasis by nearly 60%.

"If the Phase 3 trial confirms these results, it could be paradigm-shifting for cancer vaccines." — Dr. Shailender Bhatia, Fred Hutch Cancer Center

Mechanism and Safety

The vaccine uses mRNA technology to encode up to 34 neoantigens identified from each patient's tumor. It is designed to train T cells to target those specific markers. Pembrolizumab works by removing a mechanism that cancer cells use to evade immune detection.

Side effects were reported as mild, including chills and injection site pain, similar to mRNA COVID-19 vaccines.

Expert Statements

Dr. Janice Mehnert of NYU Langone noted that the vaccine appears to boost recurrence-free survival.

Other Developments in Pancreatic Cancer Treatment

Daraxonrasib

A drug called daraxonrasib has shown promise in treating pancreatic cancer. The drug targets cancer cells with a specific mutation.

In a clinical trial, patients on the drug lived 8 to 9 months without disease progression on average, compared to 2-3 months with chemotherapy. The company Revolution Medicines reported the results and stated it will seek FDA approval. Former U.S. Senator Ben Sasse reported that his tumors shrank while taking the experimental drug.

Universal KRAS Vaccine

Researchers are developing an off-the-shelf vaccine targeting the KRAS protein, which is present in up to 90% of pancreatic cancers. An early trial showed that approximately 85% of participants mounted an immune response.

Funding and Political Context

  • The National Cancer Institute (NCI) announced plans to help raise $200 million specifically for novel cancer vaccines, with mRNA vaccines as a major part of that portfolio.
  • In 2025, the White House proposed a cut of over 40% to funding for the NCI. The proposal was not implemented.
  • The U.S. Department of Health and Human Services canceled a $590 million deal with Moderna to develop an mRNA-based pandemic influenza vaccine and announced it would no longer fund mRNA research through the Biomedical Advanced Research and Development Authority (BARDA), canceling 22 contracts.
  • FDA Commissioner Dr. Marty Makary stated the agency terminated contracts to save taxpayer money, noting that companies that made mRNA vaccines earned over $50 billion.
  • Researchers reported that skepticism around COVID-19 vaccines has made recruiting for mRNA cancer vaccine trials more difficult.
  • Federal research grants have recently started to flow again after interruptions, with the NCI awarding competitive grants in March.

Next Steps

  • BioNTech and Genentech have launched a global Phase 2 trial for the pancreatic cancer vaccine, involving approximately 260 patients.
  • A Phase 3 trial for the melanoma vaccine, involving nearly 1,000 patients, has completed treatment. Results are pending analysis for potential FDA approval.
  • Researchers are studying mRNA vaccines for other cancers, such as lung cancer.

Caution

Researchers have noted that the Phase 1 pancreatic cancer trial was small and non-randomized. Results require confirmation in larger studies. Dr. Robert Vonderheide stated that there may be other factors explaining both immune response and survival.