{
  "abstract": "Adoptive cell therapy (ACT) has shown remarkable success in the treatment of some malignancies, particularly leukemia. However, there are multiple factors that limit the durability of ACT in solid tumors, including dose-limiting toxicities, the immunosuppressive tumor microenvironment, and T-cell exhaustion. As the manufacture and preparation of adoptive T-cell therapies allows time and adequate conditions for ex vivo T-cell engineering, forward genetic screens can identify novel genetic targets that could improve their effectiveness. CRISPR is a commonly used functional genomics tool that has been successfully used to both enhance our understanding of mechanisms of resistance and to discover potential genetic edits to improve ACT. A complementary approach, Sleeping Beauty transposon mutagenesis provides additional opportunities to identify novel genetic edits without being constrained by the annotated human genome. Here, we summarize forward genetic screens and their tools to uncover strategies to enhance ACT. Complementary approaches can be combined and improved on to identify translatable genetic editing strategies through studies that accurately recapitulate disease-specific challenges.",
  "authors": [
    {
      "affiliations": [
        "Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA",
        "Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota, USA",
        "Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA"
      ],
      "name": "Joseph G Skeate"
    },
    {
      "affiliations": [
        "Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA",
        "Department of Genetics, Cell Biology and Development, University of Minnesota, Twin Cities, Minneapolis, Minnesota, USA"
      ],
      "name": "Chang-Jung Lee"
    },
    {
      "affiliations": [
        "Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA",
        "T Cell Engineering Laboratory Program, Mayo Clinic, Rochester, Minnesota, USA",
        "Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, Minnesota, USA"
      ],
      "name": "Carli Stewart"
    },
    {
      "affiliations": [
        "Department of Computer Science and Engineering, University of Minnesota, Minneapolis, Minnesota, USA",
        "Graduate Program in Bioinformatics and Computational Biology (BICB), University of Minnesota, Minneapolis, Minnesota, USA",
        "Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA"
      ],
      "name": "Mathew J Fischbach"
    },
    {
      "affiliations": [
        "Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA",
        "Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota, USA",
        "Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA"
      ],
      "name": "Bibekananda Kar"
    },
    {
      "affiliations": [
        "Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USA",
        "Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, Minnesota, USA",
        "Center for Immunology, University of Minnesota, Minneapolis, Minnesota, USA"
      ],
      "name": "Alexander K Tsai"
    },
    {
      "affiliations": [
        "T Cell Engineering Laboratory Program, Mayo Clinic, Rochester, Minnesota, USA",
        "Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA",
        "Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA",
        "Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, Minnesota, USA",
        "Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA"
      ],
      "name": "Saad S Kenderian"
    },
    {
      "affiliations": [
        "Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA",
        "Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USA",
        "Department of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, Minnesota, USA"
      ],
      "name": "Ingunn M Stromnes"
    },
    {
      "affiliations": [
        "Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA",
        "Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota, USA",
        "Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA",
        "Department of Genetics, Cell Biology and Development, University of Minnesota, Twin Cities, Minneapolis, Minnesota, USA"
      ],
      "name": "David A Largaespada"
    },
    {
      "affiliations": [
        "Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA",
        "Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota, USA",
        "Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA"
      ],
      "name": "Branden S Moriarity"
    },
    {
      "affiliations": [
        "Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA",
        "Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, Minnesota, USA"
      ],
      "name": "Laura M Rogers"
    }
  ],
  "title": "Functional genomics for improving adoptive T-cell transfer therapies",
  "uid": "11c66e80-93ed-5705-bc90-037ee4f6f7c3"
}