{
  "abstract": "Background The next generation of cancer therapies requires robust in vitro testing to evaluate therapeutic efficacy and inherent toxicity. Recent reports from multiple agencies have highlighted a shift away from animal models toward biologically relevant human in vitro models. The landscape of long-term primary human tumor models has advanced significantly in recent years, providing the framework for robust ex vivo testing platforms.Methods We have established long-term tumoroid models from primary dissociated human tumors that can be propagated through multiple passages and cryopreserved without loss of viability. Using a combination of whole-exome and bulk RNA sequencing, we demonstrated that these models retain the genomic and transcriptomic profiles of the parental tumors. The broad transcriptomic findings were further refined through unbiased proteomic profiling to understand the expression patterns of known and novel drug targets and biomarkers within the tumoroid models. These models were further evaluated using standard-of-care, novel small molecule inhibitors, and next generation antibody-drug conjugates to assess differential drug responses across patient samples.Results As these tumoroid models represent the primary tumor fraction from the parent sample, we have established complementary systems to understand the additional cellular components of the tumor microenvironment. Stromal cell cultures were generated from the primary dissociated tumor samples and displayed morphology and expression patterns consistent with cancer-associated fibroblasts. Additionally, we utilized both autologous peripheral blood and tumor-infiltrating immune cells to explore the immune-tumor and immune-stroma interactions. Lastly, we evaluated the cytotoxic activities of autologous, HLA-matched peripheral blood mononuclear cells, as well as isolated NK cells and gd T cells, using a real-time imaging system.Conclusions Together, this complex ex vivo tumor model systems provide the foundation for robust and high-throughput testing of emerging targeted therapies, accelerating the development of more effective cancer treatment.",
  "authors": [
    {
      "affiliations": [
        "Discovery Life Sciences, Huntsville, AL, USA"
      ],
      "name": "Audrey Hooper"
    },
    {
      "affiliations": [
        "Discovery Life Sciences, Huntsville, AL, USA"
      ],
      "name": "Jessica Maxwell"
    },
    {
      "affiliations": [
        "Discovery Life Sciences, Huntsville, AL, USA"
      ],
      "name": "Kayla Williams"
    },
    {
      "affiliations": [
        "Discovery Life Sciences, Huntsville, AL, USA"
      ],
      "name": "Kerri Colwell"
    },
    {
      "affiliations": [
        "Discovery Life Sciences, Huntsville, AL, USA"
      ],
      "name": "Cavin Ott"
    },
    {
      "affiliations": [
        "Discovery Life Sciences, Huntsville, AL, USA"
      ],
      "name": "Jaison Arivalagan"
    },
    {
      "affiliations": [
        "Discovery Life Sciences, Huntsville, AL, USA"
      ],
      "name": "Jessica Moore"
    },
    {
      "affiliations": [
        "Discovery Life Sciences, Huntsville, AL, USA"
      ],
      "name": "Danielle Guiterrez"
    },
    {
      "affiliations": [
        "Discovery Life Sciences, Huntsville, AL, USA"
      ],
      "name": "Shawn P Fahl"
    }
  ],
  "title": "1247 Complex ex vivo tumor models to evaluate novel drug candidate responses",
  "uid": "d835bfa0-bc2f-5592-948f-48babe7b9690"
}