{
  "abstract": "Background The efficacy of immune-based therapies such as CAR-T cells is often diminished in solid tumors due to the highly immunosuppressive tumor microenvironment (TME). Comprised of immune-suppressive cells, stromal elements, and inhibitory cytokines, the TME restricts immune cell function and promotes resistance. While next-generation cell therapies seek to overcome these barriers, a critical gap remains: few preclinical models faithfully replicate the complexity of human TMEs and their influence on immune effector function.Methods Champions Oncology developed an ex vivo, patient-derived 3D co-culture system incorporating organoids from its deeply annotated biobank of over 1,500 PDX models. Tumors are selected based on molecular profiles using RNA-seq, proteomics, and phospho-proteomics. Organoids maintain phenotypic fidelity and are co-cultured with two key TME components: human cancer-associated fibroblasts (CAFs) and M2-polarized macrophages. Models are seeded in high-throughput 96-well plates and dosed with various CAR-T constructs, including untransduced, targeted, and armored formats. A custom flow cytometry panel is used to assess immune phenotypes, tumor killing, and activation states.Results The triculture platform produced stable, well-formed 3D structures representative of patient tumors. CAR-T-mediated cytotoxicity was observed across conditions, with distinct differences based on CAR-T format and presence of suppressive TME components. Armored CAR-T cells exhibited improved function in the immunosuppressive context, while combination treatments (e.g., CAR-T + checkpoint inhibitors or myeloid modulators) further enhanced response. Flow cytometry confirmed effective T cell infiltration and activation, while tumor persistence and resistance signatures could be interrogated within the same assay.Conclusions Champions Oncology’s patient-derived triculture platform represents a major advance in modeling immune suppression in solid tumors. By integrating CAFs, M2 macrophages, and tumor organoids into a single system, this model enables high-throughput, mechanistic evaluation of CAR-T therapies and combination strategies in a clinically reflective TME. It provides a scalable, physiologically relevant tool to optimize immunotherapies and advance the development of next-generation cell-based treatments for solid tumors.",
  "authors": [
    {
      "affiliations": [
        "Champions Oncology, Rockville, MD, USA"
      ],
      "name": "Fu-Ju Chou"
    },
    {
      "affiliations": [
        "Champions Oncology, Rockville, MD, USA"
      ],
      "name": "Sumanun Suwunnakorn"
    },
    {
      "affiliations": [
        "Champions Oncology, Hackensack, NJ, USA"
      ],
      "name": "Veena Jagannathan"
    },
    {
      "affiliations": [
        "Champions Oncology, Hackensack, NJ, USA"
      ],
      "name": "Brandon Walling"
    },
    {
      "affiliations": [
        "Champions Oncology, Hackensack, NJ, USA"
      ],
      "name": "Stefano Cairo"
    },
    {
      "affiliations": [
        "Champions Oncology, Hackensack, NJ, USA"
      ],
      "name": "Marianna Zipeto"
    },
    {
      "affiliations": [
        "Champions Oncology, Rockville, MD, USA"
      ],
      "name": "BanuPriya Sridharan"
    },
    {
      "affiliations": [
        "Champions Oncology, Hackensack, NJ, USA"
      ],
      "name": "Mara Gilardi"
    }
  ],
  "title": "1244 Modeling the immunosuppressive tumor microenvironment for CAR-T development: a patient-derived 3D co-culture platform with CAFs and M2 macrophages",
  "uid": "e27d9e32-e59c-57af-9297-faa66ae63c7b"
}