{
  "abstract": "Background Chimeric antigen receptor (CAR)-T cell therapy has been successful for the treatment of hematological cancers but less effective against solid tumors, a phenomenon that results from the immunosuppressive nature of the tumor microenvironment. As a strategy to improve the treatment of solid tumors, we applied CAR therapy to dendritic cells (DCs) to generate CAR-DCs. The CAR targeted the human epidermal growth factor receptor 2 (HER2) which is overexpressed in breast cancer to defeat the immunosuppressive nature of the tumor microenvironment.Methods CAR-DCs were generated by lentiviral vector transduction of SAMHD1 knock-out murine bone marrow-derived DCs. The vectors coexpressed CD40L and a soluble form of programmed cell death 1 (PD-1), a checkpoint inhibitor. To increase the durability of CAR-DCs, a gene encoding the cytokine GM-CSF was introduced into the CAR vector. The CAR-DCs were injected into mice bearing B16.HER2 melanoma tumors. Tumor growth was measured, and T cell functionality was determined by IFNγ expression and in vitro cytolytic assay.Results CAR-DCs suppressed the growth of B16.HER2 tumors and induced the proliferation and activation of tumor-infiltrating cytolytic CD8+T cells. The PD-1 checkpoint inhibitor further augmented the antitumor response and prevented T cell exhaustion. Vectored expression of GM-CSF increased the durability of the antitumor response.Conclusions CAR-DCs could be an effective strategy for therapies against solid tumors that should be further explored. The approach relies on the antigen-presenting ability of DCs and their role in T cell activation and can be coupled with checkpoint inhibition in place of monoclonal antibody treatment.",
  "authors": [
    {
      "affiliations": [
        "Department of Microbiology, NYU Grossman School of Medicine, New York, New York, USA"
      ],
      "name": "Julia Minnee"
    },
    {
      "affiliations": [
        "Department of Microbiology, NYU Grossman School of Medicine, New York, New York, USA"
      ],
      "name": "Wallace ZH Wong"
    },
    {
      "affiliations": [
        "Department of Microbiology, NYU Grossman School of Medicine, New York, New York, USA"
      ],
      "name": "Benjamin S Russell"
    },
    {
      "affiliations": [
        "Department of Microbiology, NYU Grossman School of Medicine, New York, New York, USA"
      ],
      "name": "Jose LM Semana"
    },
    {
      "affiliations": [
        "Department of Microbiology, NYU Grossman School of Medicine, New York, New York, USA"
      ],
      "name": "Ruofan Li"
    },
    {
      "affiliations": [
        "Department of Microbiology, NYU Grossman School of Medicine, New York, New York, USA"
      ],
      "name": "Nathaniel R Landau"
    },
    {
      "affiliations": [
        "Department of Microbiology, NYU Grossman School of Medicine, New York, New York, USA"
      ],
      "name": "Takuya Tada"
    }
  ],
  "title": "Chimeric antigen receptor dendritic cells suppress melanoma growth in preclinical cancer models",
  "uid": "efaec050-b483-5dae-8cfa-ece8f81ed362"
}