{
  "abstract": "Background Blinatumomab, inotuzumab or autologous anti-CD19 chimeric antigen receptor (CAR)-T cells have revolutionized the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, tumor escape through antigenic modulation accounts for almost 40% of subsequent relapses. Multi-antigen targeting strategies should be developed, and it is urgent to identify new targets.Methods We investigated the extensive immunophenotyping of 13 BCP-ALL from pediatric patients by using the BioLegend Human Cell Surface Marker Screening Kit. Then, to assess whether targeting each antigen with monoclonal antibodies could lead to leukemic cell lysis, long-term antibody-dependent cellular cytotoxicity (ADCC) assays were performed using murine monoclonal antibodies and human T cells armed with murine CD16.Results 13 highly expressed antigens were selected. With the antibodies tested here, the most significant lysis was observed by targeting CD24 and CD156c. The double targeting of CD24-CD123 appeared to be even more effective. Triple targeting was associated with a reduction in ADCC activity.Conclusion CD24 therefore emerged as an effective target in BCP-ALL, and the combination of CD24 and CD123 as a potential effective double-targeting strategy. The combination of different recognition modalities (eg, a CAR and CD16) should be tested to determine whether it provides synergistic cytotoxic activity in triple targeting.",
  "authors": [
    {
      "affiliations": [
        "Nantes Université, CHU Nantes, INSERM, pediatric hematology et oncology department, CIC 1413, F-44000 Nantes, France, University Hospital Centre Nantes, Nantes, France",
        "Nantes Université, Inserm UMR 1307, CNRS UMR 6075, CRCI2NA, Team 12, CRCINA, Nantes, France"
      ],
      "name": "Audrey Grain"
    },
    {
      "affiliations": [
        "Nantes Université, Inserm UMR 1307, CNRS UMR 6075, CRCI2NA, Team 12, CRCINA, Nantes, France"
      ],
      "name": "Jocelyn Ollier"
    },
    {
      "affiliations": [
        "Nantes Université, CHU Nantes, INSERM, pediatric hematology et oncology department, CIC 1413, F-44000 Nantes, France, University Hospital Centre Nantes, Nantes, France",
        "Nantes Université, Inserm UMR 1307, CNRS UMR 6075, CRCI2NA, Team 12, CRCINA, Nantes, France"
      ],
      "name": "Baptiste Le Calvez"
    },
    {
      "affiliations": [
        "Nantes Université, Inserm UMR 1307, CNRS UMR 6075, CRCI2NA, Team 12, CRCINA, Nantes, France"
      ],
      "name": "Elodie Guiet"
    },
    {
      "affiliations": [
        "Nantes Université, CHU Nantes, INSERM, pediatric hematology et oncology department, CIC 1413, F-44000 Nantes, France, University Hospital Centre Nantes, Nantes, France"
      ],
      "name": "Caroline Thomas"
    },
    {
      "affiliations": [
        "Nantes Université, CHU Nantes, INSERM, pediatric hematology et oncology department, CIC 1413, F-44000 Nantes, France, University Hospital Centre Nantes, Nantes, France"
      ],
      "name": "Marie-Laure Couec"
    },
    {
      "affiliations": [
        "Nantes Université, CHU Nantes, INSERM, pediatric hematology et oncology department, CIC 1413, F-44000 Nantes, France, University Hospital Centre Nantes, Nantes, France"
      ],
      "name": "Margaux Camuset"
    },
    {
      "affiliations": [
        "Nantes Université, CHU Nantes, INSERM, pediatric hematology et oncology department, CIC 1413, F-44000 Nantes, France, University Hospital Centre Nantes, Nantes, France"
      ],
      "name": "Fanny Rialland"
    },
    {
      "affiliations": [
        "Hematology Biology, University Hospital Centre Nantes, Nantes, France"
      ],
      "name": "Marion Eveillard"
    },
    {
      "affiliations": [
        "Nantes Université, Inserm UMR 1307, CNRS UMR 6075, CRCI2NA, Team 12, CRCINA, Nantes, France"
      ],
      "name": "Emmanuel Scotet"
    },
    {
      "affiliations": [
        "Nantes Université, Inserm UMR 1307, CNRS UMR 6075, CRCI2NA, Team 12, CRCINA, Nantes, France"
      ],
      "name": "Béatrice Clémenceau"
    }
  ],
  "title": "Evaluation of multi-antigen targeting ADCC strategies in pediatric BCP-ALL",
  "uid": "c419d767-6292-5120-b18d-9698d49d00b9"
}