Overview

A recent study highlights the potential of messenger RNA (mRNA)-based vaccines in combating gastric cancer metastasis, particularly in cases where the cancer spreads to the peritoneum, the lining of the abdominal cavity. Gastric cancer is a major contributor to cancer-related deaths globally, with peritoneal metastasis being the most prevalent form of recurrence following surgical interventions. Current treatment strategies, including anti-PD-1 therapies combined with chemotherapy, have shown limited success against this aggressive form of cancer.

Immunotherapy Innovations

Researchers are increasingly looking toward immunotherapy as a viable option for improving treatment outcomes. Specifically, vaccines targeting tumor-specific neoantigens (neoAgs) are gaining attention as they promise to elicit robust antitumor responses while minimizing off-target effects. A study published in the journal Gastric Cancer on July 31, 2025, reveals the development of a neoAg mRNA vaccine that exhibits notable antitumor efficacy, especially when used alongside standard anti-PD-1 therapy.

Research Overview

The research team, led by Professor Kazuhiro Kakimi from Kindai University, Japan, alongside collaborators from various prestigious institutions, synthesized the vaccine using lipid nanoparticles to encapsulate the mRNA. This mRNA is produced through in vitro transcription and includes three linked minigenes that encode neoAgs previously identified from the mouse gastric cancer cell line YTN16.

Experimental Results

The vaccine was tested in various mouse models, both alone and in combination with anti-PD-1 therapy. The results demonstrated a significant increase in neoAg-specific cytotoxic T cells compared to a similar neoAg-dendritic cell-based vaccine. In therapeutic settings, the mRNA-based vaccine led to tumor regression and complete eradication in all treated mice, with enhanced results when combined with anti-PD-1 therapy.

Understanding the Mechanism

The combined treatment's heightened efficacy can be attributed to how tumor-reactive T cells differentiate within the tumor microenvironment. Professor Kakimi explained that T cells can transition from a progenitor exhausted state to an intermediate exhausted state with robust effector function. While anti-PD-1 therapy alone increases effector cells, it fails to boost progenitor cells necessary to sustain these effects. By adding the vaccine, both cell populations are amplified, resulting in prolonged antitumor activity.

Addressing Peritoneal Metastasis

The study is particularly noteworthy for its focus on peritoneal metastasis, a historically challenging condition to treat. The vaccine demonstrated a protective effect in mice inoculated with YTN16 cells intraperitoneally and significantly reduced tumor growth in mice with established peritoneal metastases when combined with anti-PD-1 therapy.

Future Directions in Cancer Treatment

The findings contribute to the ongoing movement toward personalized cancer therapies. NeoAgs, derived from unique genetic alterations in individual patients, represent critical targets for tailored immunotherapy. However, challenges remain in accurately identifying which neoAgs are recognized and attacked by T cells in vivo. Researchers, including Professor Kakimi, are dedicated to refining the processes for predicting and identifying these vital antigens.

Industry Response

Various pharmaceutical companies are investing in the therapeutic potential of mRNA vaccines. Notably, companies like Moderna and BioNTech are conducting clinical trials that explore the efficacy of neoAg-based mRNA vaccines in conjunction with immune checkpoint inhibitors.

Conclusion

This research underscores the significant therapeutic promise of personalized mRNA vaccines in the landscape of cancer immunotherapy, paving the way for innovative, genome-informed treatment strategies.