{
  "abstract": "Background Cytokine-induced memory-like natural killer (CIML NK) cells demonstrate potent antitumor efficacy against hematological malignancies. Nevertheless, the therapeutic potential of adoptive NK cell transfer remains constrained in solid tumors due to insufficient tumor infiltration efficiency. Developing a novel tetravalent bispecific killer engager (BiKE) to modify CIML NK cells would be a promising strategy to enhance therapeutic efficacy.Methods We employed SpyTag-SpyCatcher technology to engineer tetravalent BiKEs, specifically KK-LC-1×CD16A, and to equip CIML NK cells with this protein. Flow cytometry and a luciferase reporter gene system were used to evaluate the activation and cytotoxicity of CIML NK cells. Histological analysis and in vivo real-time fluorescence imaging were employed in the xenograft tumor model to confirm the tumor-infiltrating effectiveness of KK-LC-1×CD16A-armed CIML NK cells. The in vivo antitumor efficacy of armed CIML NK cells was evaluated in subcutaneous gastric cancer xenograft models.Results We successfully developed a tetravalent NK cell engager, KK-LC-1×CD16A, which exhibits excellent binding affinity to its targets. CIML NK cells armed with this protein exhibit enhanced activation and augmented cytotoxicity against tumor cells. In xenograft tumor models, the accumulation of KK-LC-1×CD16A-armed CIML NK cells at the tumor site was significantly increased, resulting in marked suppression of tumor growth and prolonged survival in mice.Conclusion KK-LC-1×CD16A-armed CIML NK cells demonstrate significant clinical potential as a multifunctional therapeutic platform, effectively overcoming both tumor infiltration limitations and functional suppression in conventional NK cell therapies. This approach provides valuable insights for optimizing the therapeutic efficacy of CIML NK cell therapy.",
  "authors": [
    {
      "affiliations": [
        "Department of Oncology, Nanjing Drum Tower Hospital and Group's Suqian Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China",
        "Department of Oncology, China Pharmaceutical University Nanjing Drum Tower Hospital, Nanjing, Jiangsu, China"
      ],
      "name": "Mengzhu Li"
    },
    {
      "affiliations": [
        "Department of Oncology, Nanjing Drum Tower Hospital and Group's Suqian Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China"
      ],
      "name": "Tianran Chen"
    },
    {
      "affiliations": [
        "Department of Oncology, Nanjing Drum Tower Hospital and Group's Suqian Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China"
      ],
      "name": "Siwen Wu"
    },
    {
      "affiliations": [
        "Department of Oncology, Nanjing Drum Tower Hospital and Group's Suqian Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China"
      ],
      "name": "Yuxiang Li"
    },
    {
      "affiliations": [
        "Department of Oncology, Nanjing Drum Tower Hospital and Group's Suqian Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China"
      ],
      "name": "Qin Liu"
    },
    {
      "affiliations": [
        "Department of Oncology, Nanjing Drum Tower Hospital and Group's Suqian Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China"
      ],
      "name": "Ying Wang"
    },
    {
      "affiliations": [
        "Department of Oncology, Nanjing Drum Tower Hospital and Group's Suqian Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China",
        "Department of Oncology, China Pharmaceutical University Nanjing Drum Tower Hospital, Nanjing, Jiangsu, China"
      ],
      "name": "Jingyi Guo"
    },
    {
      "affiliations": [
        "Department of Oncology, Nanjing Drum Tower Hospital and Group's Suqian Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China",
        "Department of Oncology, China Pharmaceutical University Nanjing Drum Tower Hospital, Nanjing, Jiangsu, China"
      ],
      "name": "Lanqi Cen"
    },
    {
      "affiliations": [
        "Department of Oncology, Nanjing Drum Tower Hospital and Group's Suqian Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China"
      ],
      "name": "Lu Zou"
    },
    {
      "affiliations": [
        "Department of Oncology, Nanjing Drum Tower Hospital and Group's Suqian Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China"
      ],
      "name": "Manman Tian"
    },
    {
      "affiliations": [
        "Department of Oncology, Nanjing Drum Tower Hospital and Group's Suqian Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China"
      ],
      "name": "Wenxiu Chen"
    },
    {
      "affiliations": [
        "Department of Oncology, Nanjing Drum Tower Hospital and Group's Suqian Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China"
      ],
      "name": "Rutian Li"
    },
    {
      "affiliations": [
        "Department of Oncology, Nanjing Drum Tower Hospital and Group's Suqian Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China"
      ],
      "name": "Jie Shen"
    },
    {
      "affiliations": [
        "Department of Oncology, Nanjing Drum Tower Hospital and Group's Suqian Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China",
        "Department of Oncology, China Pharmaceutical University Nanjing Drum Tower Hospital, Nanjing, Jiangsu, China"
      ],
      "name": "Baorui Liu"
    },
    {
      "affiliations": [
        "Department of Oncology, Nanjing Drum Tower Hospital and Group's Suqian Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China"
      ],
      "name": "Jie Shao"
    }
  ],
  "title": "Novel tetrameric bispecific KK-LC-1×CD16A-armed memory-like NK cells enhance antitumor efficacy in gastric cancer",
  "uid": "a7dca236-5904-5673-b638-b66d14ab72b7"
}