A new study from Memorial Sloan Kettering Cancer Center has shown that an RNA-based neoantigen vaccine can generate long-lasting immune cells that may help slow the recurrence of pancreatic ductal adenocarcinoma (PDAC)—one of the deadliest cancers.
The findings, published in Nature, suggest that this personalized cancer vaccine can stimulate CD8+ T cells, a type of immune cell that fights cancer, potentially improving survival rates for patients with this aggressive disease.
Why This Matters
Pancreatic cancer is one of the most difficult cancers to treat, with limited treatment options and a low survival rate. One reason for this is that pancreatic tumors don’t have many mutations, making them hard for the immune system to recognize and attack.
Traditional cancer vaccines have struggled to create strong, long-lasting immune responses. This study aimed to test whether an mRNA-based neoantigen vaccine could train the immune system to recognize and destroy cancer cells more effectively.
How the Study Was Done
The Phase I clinical trial tested an individualized mRNA vaccine called autogene cevumeran in 16 patients with pancreatic cancer who had undergone surgery. The vaccine was designed to target up to 20 unique neoantigens (mutated proteins found in tumor cells).
Patients received the vaccine as part of a treatment plan that also included:
- Surgery to remove the tumor
- Atezolizumab, a type of immunotherapy
- Chemotherapy (12 cycles of a drug regimen called mFOLFIRINOX)
- A booster dose of the vaccine
Researchers tracked immune responses using blood tests, genetic sequencing, and immune cell analysis over a median follow-up period of 3.2 years.
Key Findings
- Half of the vaccinated patients (8 out of 16) developed strong CD8+ T cell responses against their tumor’s neoantigens. These patients—called responders—had a much lower risk of cancer returning.
- By the end of the study, most responders had not experienced a recurrence, meaning they survived longer than expected. In comparison, non-responders had a median survival of 13.4 months before their cancer came back.
- The vaccine-induced T cells expanded rapidly in responders—by an average of 100 times—after just a few doses.
- These T cells persisted in the body for years, with an estimated lifespan of 7.7 years post-vaccination.
- About 86% of these immune cells remained active for at least three years, and some may persist for decades.
- The T cells transitioned into memory-like immune cells that retained their ability to kill cancer cells, even when tested 3.6 years after vaccination.
However, some patients who relapsed had tumors that had lost the specific mutations targeted by the vaccine—suggesting that cancer cells can evolve to escape immune detection. This highlights the need for further research to prevent tumors from becoming resistant to treatment.
What This Means for Cancer Treatment
This study shows, for the first time in pancreatic cancer, that an mRNA-based vaccine can trigger a strong, long-lasting immune response against tumors.
While the study was small, the results suggest that this type of vaccine could improve survival for pancreatic cancer patients by delaying or preventing cancer recurrence. If larger trials confirm these findings, this approach could be applied to other hard-to-treat cancers as well.
Next Steps
- Larger clinical trials are needed to confirm how well this vaccine works and how many patients benefit.
- Researchers need to find ways to increase the number of responders and reduce the chances of tumors escaping immune detection.
- Future studies could explore whether combining this vaccine with other immunotherapies might improve outcomes further.
This study marks a major step forward in personalized cancer treatment and offers new hope for one of the world’s most challenging cancers.
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The study is published in Nature.
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