{
  "abstract": "Background mRNA cancer vaccines represent a next-generation immunotherapy platform with the potential to elicit robust, antigen specific immune responses. Upon in vivo delivery, mRNA vaccines are taken up by antigen-presenting cells (APCs),translated into the tumor associated antigen and presented via MHC molecules to activate adaptive immunity. However, standard mouse models with murine MHC molecules are not suitable for evaluating these MHC-restricted immune responses.Methods GemPharmatech has developed a series of MHC knock-in (KI) models across multiple mouse backgrounds including immunocompetent mice B6, BALB/c, CB6F1 and immunodeficient NCG derived mice. These models express human HLA molecules, enabling the accurate evaluation of antigen presentation, immunogenicity, and therapeutic efficacy of mRNA vaccines.Results MHC KI mice exhibited strain specific humoral and cellular immune responses, but are sufficient to satisfy various evaluation needs. CB6F1 exhibited good combination of humoral and cellular immune response to the same immunogen, making them more suitable for assessing vaccine immunogenicity. In NCG-M-hHLA-A2.1 mice engrafted with hematopoietic stem cells, HLA-A2.1-restricted immune responses were observed, reflecting successful reconstitution of human DCs and functional T cells. Therapeutic studies using TA-1 (mRNA vaccine) or anti-PD1 in a patient derived xenograft (PDX) demonstrated that TA-1 or anti-PD-1 inhibited tumor growth, while combination therapy led to greater tumor inhibition.Additionally, we established adoptive cell transfer models, in which splenocytes from immunized immunocompetent MHC KI mice were injected into HLA-matched, tumor bearing immunodeficient mice. This approach enables a time and cost-effective method for the evaluation of mRNA vaccines targeting human tumor associated antigens without requiring genetically modified tumor cell lines.Conclusions GemPharmatech’s diverse portfolio of MHC knock-in mouse models provide more versatile and translationally relevant platforms for preclinical testing of mRNA-based cancer vaccines and combination immunotherapies. These models bridge the gap between murine and human immune systems, enhancing predictive power in vaccine development pipelines.",
  "authors": [
    {
      "affiliations": [
        "GePharmatech Co., Ltd., Nanjing, China"
      ],
      "name": "Jialu Fan"
    },
    {
      "affiliations": [
        "GePharmatech Co., Ltd., Nanjing, China"
      ],
      "name": "Yunlong Jiang"
    },
    {
      "affiliations": [
        "GePharmatech Co., Ltd., Nanjing, China"
      ],
      "name": "Hongyan Sun"
    },
    {
      "affiliations": [
        "GePharmatech Co., Ltd., Nanjing, China"
      ],
      "name": "Jianming Xu"
    },
    {
      "affiliations": [
        "GePharmatech Co., Ltd., Nanjing, China"
      ],
      "name": "Xiang Gao"
    }
  ],
  "title": "938 MHC knock-in mouse models for preclinical evaluation of cancer mRNA vaccines",
  "uid": "9c3adb52-dc45-5a10-8418-4e45590dca0e"
}