{
  "abstract": "Background We explored an innovative cancer immunotherapy approach designed to suppress tumor growth and extend the lifespan of tumor-bearing mice. This strategy introduces pathogen antigens into tumors via mRNA-lipid nanoparticles, leveraging pre-existing immunity to enhance therapeutic efficacy. 1 Our goal was to determine if mRNA-based vaccines could tag tumor cells with pathogen antigens and mobilize pre-existing immune responses to eliminate cancer cells. Specifically, we investigated whether prior immunization with the BNT162b2 COVID-19 vaccine would enhance the anti-tumor response against tumors tagged with the same protein.Methods The study utilized multiple tumor models in mice. Mice previously immunized with BNT162b2, encoding the SARS-CoV-2 spike protein, received intratumoral injections of the same vaccine. We measured tumor growth suppression, lifespan extension, mobilization of memory immunity, reprogramming of the tumor microenvironment, and tumor antigen-specific T-cell responses. Statistical analyses were conducted to evaluate the significance of the findings.Results Intratumoral injections of BNT162b2 in previously immunized mice tagged tumor cells with the mRNA-expressed spike protein. This rapidly mobilized pre-existing memory immunity against SARS-CoV-2, leading to the elimination of cancer cells displaying the spike protein and reprogramming of the tumor microenvironment by attracting immune cells. Partial elimination of tumor cells in a normalized microenvironment triggered extensive tumor antigen-specific T-cell responses through antigen spreading, resulting in potent systemic tumor-targeting immune responses. Combining BNT162b2 treatment with anti-PD-L1 therapy yielded a substantial therapeutic impact, even in ‘cold tumors’ typically less responsive to treatment.Conclusions Leveraging pre-existing immunity against pathogen antigens via mRNA-based vaccines, such as BNT162b2, significantly enhances cancer immunotherapy efficacy. Given widespread memory immunity against various pathogens from prior infections or vaccinations, this approach could rapidly transition into clinical use. mRNA vaccines against other pathogens, such as HBV, common human coronaviruses, and influenza virus, hold great potential for treating different cancers and overcoming drug resistance, providing a promising alternative for cancer patients.Reference Li R, Hu JC, Rong L, He Y, Wang X, Lin X, Li W, Wu Y, Kuwentrai C, Su C, Yau T, Hung IF, Gao X, Huang JD. The guided fire from within: intratumoral administration of mRNA-based vaccines to mobilize memory immunity and direct immune responses against pathogen to target solid tumors. Cell Discov. 2025;10:Article 127. doi: 10.1038/s41421-024-00743-3.Ethics Approval The study obtained ethics approval.",
  "authors": [
    {
      "affiliations": [
        "The University of Hong Kong, Pokfulam, Hong Kong, China"
      ],
      "name": "Renhao Li"
    },
    {
      "affiliations": [
        "University of Hong Kong, Hong Kong, China"
      ],
      "name": "Jiandong Huang"
    }
  ],
  "title": "638 Harnessing pre-existing pathogen immunity for enhanced cancer treatment through mRNA vaccines",
  "uid": "bc020781-fa24-5a52-81a7-d62bce8f6055"
}