Pancreatic cancer is no longer untreatable? Research reveals: A new personalized vaccine brings a turning point!

Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with a very poor prognosis. It is difficult to diagnose early and has limited treatment options, posing a huge threat to patients' health. In recent years, with the significant progress of immunotherapy in the field of cancer treatment, especially the development of personalized vaccines targeting tumor-specific antigens, new hope has been brought to the treatment of PDAC.
Recently, a study published in Nature explored the potential application of a new antigen mRNA-lipoplex vaccine derived from somatic mutations in the treatment of PDAC, comprehensively evaluated its safety and effectiveness, and analyzed the characteristics of the immune response induced by the vaccine. Through this study, it is hoped that a more precise and effective treatment strategy will be provided for PDAC patients, contributing to improving the prognosis of patients and improving their quality of life.

Research Process

This study used a uridine-based mRNA-lipoplex vaccine designed specifically for somatic mutation-derived neoantigens in PDAC patients. In the Phase I clinical trial, 19 PDAC patients who had undergone surgical resection were recruited and randomly divided into a vaccination group and a control group to ensure the fairness of the trial and the comparability of the results. Patients in the vaccination group not only received immunotherapy with atezolizumab (a PD-L1 inhibitory antibody) after surgery to relieve the immune suppression of tumor cells, but also received a personalized mRNA-lipoplex vaccine, while the control group received only standard treatment.

Subsequently, the study entered the long-term follow-up phase. During this phase, the researchers closely followed up the patients in the vaccine group for up to 3.2 years, and recorded and analyzed their RFS (recurrence-free survival: the time interval from the start of treatment to tumor recurrence, distant metastasis, or patient death) and OS (overall survival: the time interval from the start of treatment to patient death) in detail to comprehensively evaluate the long-term efficacy of the vaccine. At the same time, the study also deeply analyzed the characteristics of the vaccine-induced immune response, including the type, number, activation, and persistence of immune cells, in order to reveal the mechanism of action and potential advantages of the vaccine.
Study Results

1. Safety and effectiveness

Phase I clinical trials showed that the vaccination group had good safety and no serious adverse reactions. In terms of RFS, the vaccination group was significantly better than the control group (median RFS not reached vs. 13.4 months, P=0.007); at the same time, OS showed a trend of extension, but further data is needed to confirm its statistical significance.

2. Vaccine-induced immune response

The study found that the vaccinated group induced a high-intensity, multifunctional CD8 effector T cell response against new antigens. Simply put, after vaccination with the mRNA-lipoplex vaccine, the human body produced a large number of powerful immune cells that can more effectively identify and attack tumor cells, providing new hope for cancer treatment. Using CloneTrack technology (used to monitor the expansion of vaccine-induced T cell clones), the researchers tracked the origin and lifespan of vaccine-induced T cell clones and found that these clones have an estimated lifespan of many years, and nearly a quarter of the clones are estimated to have a lifespan of decades. At the same time, vaccine-induced T cell clones can maintain the ability to accurately strike tumor cells for up to 3.6 years after vaccination.

3. Vaccine immunity and cancer recurrence

During long-term follow-up, two vaccinated patients experienced relapse. The study found that the vaccine immunity of these two patients was weak and the cumulative vaccine immunity was low. In addition, the researchers analyzed the mutation spectrum of recurrent PDAC and found that vaccine-induced T cells target subclinical cancer clones, and one mechanism of vaccine resistance may be clonal escape. Simply put, although vaccines can induce immune responses to attack cancer cells to a certain extent, in some patients, cancer may still recur due to insufficient vaccine immunity or escape mechanisms of cancer cells. This provides important research clues for future improvements in vaccine design and treatment strategies.

Future Outlook

This study provides new ideas and methods for the treatment of PDAC. Personalized mRNA vaccines show potential application value in improving RFS and OS of PDAC patients. In the future, it is necessary to further expand the sample size and conduct multicenter, randomized, controlled Phase III clinical trials to verify the conclusions of this study. We look forward to further research to bring more good news, making this vaccine a new option for the treatment of pancreatic ductal adenocarcinoma, bringing hope to more patients, and helping to achieve new breakthroughs in cancer treatment.

References:

Sethna Z, et al. RNA neoantigen vaccines prime long-lived CD8 T cells in pancreatic cancer+. Nature (2025).

https://doi.org/10.1038/s41586-024-08508-4+