promising Advances in mRNA Vaccines for Treating Gastric Cancer Metastasis

Gastric cancer remains one of the leading causes of cancer-related deaths worldwide, with peritoneal metastasis being a common recurrence after surgical removal of the primary tumor. This form of spread to the lining of the abdominal cavity is particularly challenging to treat and is associated with poor patient survival. Current therapies, including anti-PD-1 immunotherapy combined with chemotherapy, have shown limited effectiveness against peritoneal dissemination.

Recent research highlights the potential of immunotherapy, especially vaccines targeting tumor-specific neoantigens, to generate more durable antitumor responses with fewer side effects. A groundbreaking study published in the journal Gastric Cancer on July 31, 2025, reports the development of a neoantigen (neoAg) mRNA-based vaccine demonstrating strong antitumor activity against gastric cancer cells, especially when used together with standard anti-PD-1 therapy.

Led by Professor Kazuhiro Kakimi from Kindai University, Japan, the research team included experts from various institutions, including Dr. Koji Nagaoka. Their innovative vaccine uses lipid nanoparticles (LNPs) to deliver synthesized mRNA encoding three neoantigens identified from a mouse gastric cancer cell line. These neoantigens are linked in a single mRNA molecule created via in vitro transcription.

In preclinical trials using mouse models, both alone and in combination with anti-PD-1 therapy, the vaccine performed remarkably well. It elicited a higher frequency of neoantigen-specific cytotoxic T cells compared to dendritic cell-based vaccines and induced tumor regression and eradication in treated mice—effects that were significantly enhanced when combined with immune checkpoint inhibition.

The efficacy hinges on the differentiation of tumor-reactive T cells within the tumor environment. Combining the vaccine with anti-PD-1 therapy increased both progenitor-exhausted (Tex
prog) and effector (Tex
int) T cell populations, sustaining a potent antitumor response. Notably, the vaccine showed promise against peritoneal metastases, reducing tumor growth even after metastasis was established, a feat that has posed significant challenges historically.

This research underscores the potential of personalized mRNA vaccines in cancer treatment, targeting neoantigens derived from each patient’s unique tumor mutations. Despite hurdles such as identifying the most effective neoantigens, global pharmaceutical giants like Moderna and BioNTech are advancing neoAg-based mRNA vaccines into clinical trials, often combined with checkpoint inhibitors.

These findings mark a significant step toward next-generation, personalized cancer immunotherapies, offering hope for more effective treatments for advanced gastric cancer and its metastases.