{
  "abstract": "Background Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapy for patients with refractory or relapsed lymphoma or leukemia. However, inefficient activity and insufficient persistence of CAR T cells impede the durability of its therapeutic efficacy.Methods Krüppel-like factor 4 (KLF4)-overexpressing CAR T cells were generated and assessed for function, exhaustion, and transcriptional changes using in vitro stimulation models and RNA sequencing, with antitumor efficacy validated in mouse models.Results We report that KLF4 overexpression enhances the durability of CAR T-cell antitumor efficacy. KLF4 overexpression enhanced CAR T-cell activity and promoted the differentiation into effector CAR T cells. Furthermore, KLF4 overexpression prevented CAR T-cell exhaustion induced by continuous tumor antigen stimulation. RNA sequencing data confirmed that KLF4 overexpression led to the upregulation of genes involved in effector functions and the downregulation of genes associated with exhaustion in CAR T cells. Notably, KLF4-overexpressing CAR T cells delayed tumor growth, prolonged the survival of mice with hematological malignancies, and exhibited reduced exhaustion and enhanced effector functions in vivo relative to normal CAR T cells.Conclusions Our findings highlight the potential of KLF4 overexpression as a therapeutic approach to counteract CAR T-cell exhaustion and enhance antitumor activity, underscoring its therapeutic promise in clinical immunotherapy.",
  "authors": [
    {
      "affiliations": [
        "School of Pharmacy, Anhui Medical University, Hefei, China"
      ],
      "name": "Haoqi Wang"
    },
    {
      "affiliations": [
        "School of Pharmacy, Anhui Medical University, Hefei, China"
      ],
      "name": "Xianglong Meng"
    },
    {
      "affiliations": [
        "Department of Hematology, the First Affiliated Hospital of USTC, Anhui Provincial Cancer Hospital, Hefei, China"
      ],
      "name": "Yuanyuan Feng"
    },
    {
      "affiliations": [
        "School of Pharmacy, Anhui Medical University, Hefei, China"
      ],
      "name": "Anqi Su"
    },
    {
      "affiliations": [
        "School of Pharmacy, Anhui Medical University, Hefei, China"
      ],
      "name": "Wentao Qin"
    },
    {
      "affiliations": [
        "School of Pharmacy, Anhui Medical University, Hefei, China"
      ],
      "name": "Junjie Shen"
    },
    {
      "affiliations": [
        "School of Pharmacy, Anhui Medical University, Hefei, China"
      ],
      "name": "Kunyu Lu"
    },
    {
      "affiliations": [
        "School of Pharmacy, Anhui Medical University, Hefei, China"
      ],
      "name": "Lingling Gu"
    },
    {
      "affiliations": [
        "School of Life Sciences, Anhui Medical University, Hefei, China"
      ],
      "name": "Yujie Ma"
    },
    {
      "affiliations": [
        "School of Pharmacy, Anhui Medical University, Hefei, China"
      ],
      "name": "Yaxing Wang"
    },
    {
      "affiliations": [
        "School of Pharmacy, Anhui Medical University, Hefei, China"
      ],
      "name": "Yuqing Mao"
    },
    {
      "affiliations": [
        "Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, China"
      ],
      "name": "Dongdong Ji"
    },
    {
      "affiliations": [
        "Department of Clinical Laboratory, the First Affiliated Hospital of Anhui Medical University, Hefei, China"
      ],
      "name": "Lu Zong"
    },
    {
      "affiliations": [
        "Department of Clinical Laboratory, the First Affiliated Hospital of Anhui Medical University, Hefei, China"
      ],
      "name": "Meijuan Zheng"
    },
    {
      "affiliations": [
        "Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, China"
      ],
      "name": "Yingying Du"
    },
    {
      "affiliations": [
        "School of Pharmacy, Anhui Medical University, Hefei, China",
        "Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, China"
      ],
      "name": "Jingjing Cong"
    },
    {
      "affiliations": [
        "School of Life Sciences, Anhui Medical University, Hefei, China"
      ],
      "name": "Jing Li"
    },
    {
      "affiliations": [
        "School of Pharmacy, Anhui Medical University, Hefei, China",
        "Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, China"
      ],
      "name": "Xuefu Wang"
    }
  ],
  "title": "KLF4 overexpression in CAR T cells enhances antitumor potency by preventing exhaustion",
  "uid": "3bf12508-cb1c-5f38-9559-d63e39a03ad3"
}