Gastric cancer is one of the main causes of mortality linked to cancer worldwide, and peritoneal metastases, in which cancer spreads to the peritoneum or the mucosa of the abdominal cavity, represents the most common form of recurrence after gastric cancer surgery.
This form of metastases is particularly associated with poor survival results, as current first-line treatment options, including anti-PD-1 therapy combined with chemotherapy, have proven to be ineffective against peritoneal dissemination.
Immunotherapy has an attractive option to combat this difficult condition, more specifically, vaccines that target antigens specific to tumors called neoantigen (neoags) are explored as an option to generate lasting anti -tumor responses in patients, with less target effects.
Now in a study published online in the journal Gastric cancer On July 31, 2025, a team of researchers led by Professor Kazuhiro Kakimi, Department of Immunology, Kindai University, Faculty of Medicine, Japan, including Dr Koji Nagaoka, from the same university; Dr. Hidetaka Akita, Graduate School of Pharmaceutical Sciences, Tohoku University; Dr Keiji Itaka, Center for Infectious Disease Education and Research, University of Osaka; And Dr. Tatsuhiko Kodama, research center for advanced sciences and technology, the University of Tokyo, has developed a vaccine based on mRNA (messenger RNA) which shows powerful anti-tuthical efficiency against gastric cancer cells, in particular in combination with standard anti-PD-1 therapy.
This vaccine consists of mRNA encapsulated in lipid nanoparticles (LNP) – This mRNA is synthesized by in vitro Transcription and includes three linked minigens, which codes for three neoags which they previously identified from the cellular line of gastric cancer of the YTN16 mouse. Once the vaccine is synthesized, they proceeded to test it, both alone and in combination with anti-PD-1 therapy, in various mouse models.
The results were very promising, the vaccine has induced a higher frequency of cytotoxic cells specific to neoag in mice in a cellular vaccine based on similar dentritical-dendritic. During tests in a therapeutic context, mRNA-based vaccination led to tumor regression and eradication in all treated mice, and this effect was improved in combination with anti-PD-1 therapy.
How to explain the increased anti -tumor efficiency of this combined treatment? The key lies in the way in which T lymphocytes reactive to tumors undergo differentiation in the tumor-professional environment. Kakimi develops that they ” progress of an exhausted anchoring state (Texprogramme), through an intermediate exhausted state (Texint) with a strong effective function, and finally in an exhausted state in terminal phase (Texterm).«
While the treatment with only anti-PD-1 therapy has led to an increase in the effector (Texint) Cells, there was no corresponding increase in the production of the ancestor (Texprogramme) cells necessary to maintain these effective cells. On the other hand, by combining anti-PD-1 therapy with the vaccine that develops Texprogramme Cells, the two populations have increased, resulting in a sustained antitumor effect.
More promising, the vaccine shows an impressive anti -tumor efficiency against peritoneal metastases, which has always been very difficult to treat. The vaccine alone has shown a protective effect in mice that have been inoculated intraperitoneal with YTN16 cells. In combination with anti-PD-1 therapy, it has been shown to reduce tumor growth even in mice with already established peritoneal metastases.
These results are particularly exciting in the context of the thrust to the treatment of “personalized”, “personalized” cancer.
Neoags, derived from individual genetic alterations in each cancer patient, serve as unique immunological targets on tumor cells and represent the key to personalized immunotherapy. “”
Kazuhiro Kakimi, professor, Immunology Department, University of Kindai
However, certain challenges remain. Professor Kakimi said that ” Although we have observed that these vaccines had remarkable therapeutic efficiency, the biggest challenge lies in the identification of true neoags which are recognized and attacked by the cells t in vivo. «
Researchers from around the world, whose Kakimi teacher is currently trying to improve the process of predicting and identification of these neoantigens. However, several pharmaceutical companies are betting on the therapeutic potential of these vaccines for the body, Moderna and Biontech carry out clinical trials that use various arnm vaccines based on neoag in combination with immune control point inhibitors.
This study demonstrates the immense therapeutic potential presented by personalized cancer vaccines that use mRNA technology, opening the way to the next generation of immunotherapy against genome cancer!
