{
  "abstract": "Background Hepatocellular carcinoma (HCC), the most prevalent form of primary liver cancer, is a life-threatening malignancy with limited therapeutic options. While immune checkpoint inhibitors have emerged as a promising avenue in HCC treatment, the clinical efficacy is hampered by the low responsive rates and insufficient specificity. Messenger RNA (mRNA) vaccines, a cutting-edge immunotherapeutic modality, have gained attention for the good tolerability, rapid degradation, coupled with the ability to enhance immune responses. Our previous research revealed that Nidogen-1(NID1), a glycoprotein prominently expressed in liver tumors and circulating small extracellular vesicles of HCC patients, plays a pivotal role in promoting HCC progression and metastasis.Methods Murine NID1-mRNA vaccine was designed and constructed based on a novel lipid nanoparticle (LNP)-based delivery system. The immunogenicity of NID1-mRNA vaccine was evaluated at cellular and animal levels. The therapeutic and preventive efficacy, along with the safety profile, of the vaccine were systematically evaluated using an orthotopic tumor implantation model.Results Full-length murine NID1 mRNA was incorporated into a novel LNP formulation, and both the uptake of the vaccine and the expression of the NID1 protein by bone marrow derived dendritic cell (BMDC) was validated. NID1-mRNA vaccine remarkably induced the immunogenicity both at cellular and animal levels. NID1-mRNA vaccine demonstrated significant therapeutic and preventive effects against HCC development at the dosage of 5μg and 1μg respectively. Circulating anti-NID1 antibody levels were upregulated, with a concomitant decrease in NID1 protein concentration in vaccinated mice compared to the PBS or LNP treated mice. Toxicity evaluations demonstrated that NID1-mRNA vaccine didn’t affect the viability of the BMDC and no adverse effects were observed in the animals.Conclusions In summary, a murine NID1 encoding mRNA vaccine was established and characterized. The NID1-mRNA vaccine simultaneously elicits both cellular and humoral immune responses. In vivo evidence confirmed the vaccine’s dual therapeutic and preventive efficacy against HCC, while exhibiting negligible systemic toxicity.",
  "authors": [
    {
      "affiliations": [
        "Institute of Chinese Medical Sciences, Macau, Macau, China"
      ],
      "name": "Lu Xia"
    },
    {
      "affiliations": [
        "Institute of Chinese Medical Sciences, Macau, Macau, China"
      ],
      "name": "Tingmao Xue"
    },
    {
      "affiliations": [
        "The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, China"
      ],
      "name": "Jia Liu"
    },
    {
      "affiliations": [
        "The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, China"
      ],
      "name": "Heng Xia"
    },
    {
      "affiliations": [
        "The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, China"
      ],
      "name": "Zhijie Xiao"
    },
    {
      "affiliations": [
        "The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, China"
      ],
      "name": "Gaofeng Zha"
    },
    {
      "affiliations": [
        "Institute of Chinese Medical Sciences, Macau, Macau, China"
      ],
      "name": "Xiaowen Mao"
    }
  ],
  "title": "114 The development and application of Nidogen 1-mRNA vaccine in liver cancer therapy",
  "uid": "55d8775e-a65c-5c7e-965e-3d798d20d215"
}