{
  "abstract": "Background Cancer immunotherapies have significantly improved treatment efficacy and patient survival by exploiting antigen-specific T cells to eliminate cancer cells. However, current approaches for identifying and isolating antigen-specific T cells typically require prior knowledge of target antigens, limiting discovery, and reducing the ability to consistently detect rare tumor-reactive T cells. We therefore sought to develop an unbiased platform for the identification and enrichment of antigen-specific T cells using naturally processed and presented tumor antigens.Methods We developed ATTACH (Assessment of T cells Tethered to Antigen Class I Histocompatibility), a microfluidic platform that applies controlled shear stress and leverages tumor cells as a natural source of endogenous major histocompatibility complex (MHC)-peptide complexes to isolate antigen-specific T cells based on MHC/peptide binding avidity. ATTACH was evaluated in both human and mouse systems for its ability to enrich rare tumor-reactive T-cell populations and deplete bystander virus-specific T cells.Results ATTACH resulted in up to a 10-fold enrichment of antigen-specific T cells across both human and mouse systems, enabling the isolation of clonotypes present at frequencies as low as 0.1%. In addition to enriching rare tumor-reactive T cells, ATTACH efficiently depleted virus-specific bystander T cells.Conclusions ATTACH provides a streamlined and unbiased approach for the rapid identification and isolation of antigen-specific T cells, and may facilitate the optimization of cellular therapies for the treatment of solid tumors.",
  "authors": [
    {
      "affiliations": [
        "Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Amanda Montoya"
    },
    {
      "affiliations": [
        "Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Meredith L Frank"
    },
    {
      "affiliations": [
        "Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Peixin Jiang"
    },
    {
      "affiliations": [
        "Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Hui Nie"
    },
    {
      "affiliations": [
        "Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Minying Zhang"
    },
    {
      "affiliations": [
        "Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Emily Bontekoe"
    },
    {
      "affiliations": [
        "Deparrtment of Computer Science, Rice University, Houston, Texas, USA"
      ],
      "name": "Jared K Slone"
    },
    {
      "affiliations": [
        "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Ludovica L Posta"
    },
    {
      "affiliations": [
        "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Sofia Rosy Caterina Sorice"
    },
    {
      "affiliations": [
        "Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Tina Cascone"
    },
    {
      "affiliations": [
        "Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Maura Gillison"
    },
    {
      "affiliations": [
        "Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Don L Gibbons"
    },
    {
      "affiliations": [
        "Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA",
        "Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Jianjun Zhang"
    },
    {
      "affiliations": [
        "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Eleonora Dondossola"
    },
    {
      "affiliations": [
        "Deparrtment of Computer Science, Rice University, Houston, Texas, USA"
      ],
      "name": "Lydia Kavraki"
    },
    {
      "affiliations": [
        "The University of Texas Health Science Center, Houston, Texas, USA"
      ],
      "name": "Pamela L Wenzel"
    },
    {
      "affiliations": [
        "Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "John V Heymach"
    },
    {
      "affiliations": [
        "Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA"
      ],
      "name": "Alexandre Reuben"
    }
  ],
  "title": "Unbiased avidity-based isolation of antigen-specific T cells",
  "uid": "567501cd-f63f-5270-bb01-85275227f3b4"
}