{
  "abstract": "Background The immunologically “cold” microenvironment of triple-negative breast cancer presents a major obstacle to treatment, conferring resistance to current immunotherapies. Targeting the stimulator of interferon genes (STING) pathway has emerged as a promising strategy to enhance immunotherapy efficacy.Methods In this preclinical study, we leveraged a novel integrated approach by employing a B7-H3-targeted dual-payload antibody-drug conjugate (ADC) to induce innate immune responses and reprogram the tumor microenvironment.Results Our preliminary results indicated that the dual-payload ADC induces immunogenic cell death, leading to the release of double-stranded DNA and subsequent activation of the cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) synthase-STING pathway in macrophages and dendritic cells. This, in turn, promotes dendritic cell maturation, M1 macrophage polarization, and enhanced T-cell infiltration, effectively converting immunologically “cold” tumors into “hot” ones. Most importantly, the synergistic combination of the dual-payload ADC with immune checkpoint inhibitors (PD-L1 and 4–1BB) not only rapidly bridges innate and adaptive immunity but also elicits a robust long-term immune memory response.Conclusions Collectively, these preliminary results demonstrate that the antitumor efficacy of the dual-payload ADC is mediated through STING pathway activation. This insight opens new avenues for enhancing immunotherapy in B7-H3-expressing solid tumors and paves the way for the clinical translation of next-generation ADC designs.",
  "authors": [
    {
      "affiliations": [
        "Department of Breast Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China",
        "Department of Medical Oncology, Anhui Provincial Cancer Hospital, Hefei, Anhui, China"
      ],
      "name": "Jing Pan"
    },
    {
      "affiliations": [
        "Department of Breast Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China",
        "Department of Medical Oncology, Anhui Provincial Cancer Hospital, Hefei, Anhui, China"
      ],
      "name": "Xiaolong Yuan"
    },
    {
      "affiliations": [
        "Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China"
      ],
      "name": "Haiyang Yu"
    },
    {
      "affiliations": [
        "College of life sciences, Wuhan University, Wuhan, Hubei, China"
      ],
      "name": "Ziqi Liu"
    },
    {
      "affiliations": [
        "Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China"
      ],
      "name": "Shi Chen"
    },
    {
      "affiliations": [
        "Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China"
      ],
      "name": "Fang Zhu"
    },
    {
      "affiliations": [
        "Department of Research and Development, Anhui Genebiol Biotech. Ltd, Hefei, Anhui, China"
      ],
      "name": "Yuhua Shang"
    },
    {
      "affiliations": [
        "Department of Breast Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China",
        "Department of Medical Oncology, Anhui Provincial Cancer Hospital, Hefei, Anhui, China"
      ],
      "name": "Shikai Hong"
    },
    {
      "affiliations": [
        "Department of Breast Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China"
      ],
      "name": "Xinghua Han"
    },
    {
      "affiliations": [
        "Department of Breast Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China",
        "Department of Medical Oncology, Anhui Provincial Cancer Hospital, Hefei, Anhui, China"
      ],
      "name": "Zhengzhi Zhu"
    },
    {
      "affiliations": [
        "Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China",
        "Department of Infectious Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, University of Science and Technology of China, Hefei, Anhui, China",
        "Biomedical Sciences and Health Laboratory of Anhui Province, University of Science & Technology of China, Hefei, Anhui, China",
        "Clinical Research Hospital of Chinese Academy of Sciences (Hefei), University of Science and Technology of China, Hefei, Anhui, China"
      ],
      "name": "Tengchuan Jin"
    },
    {
      "affiliations": [
        "Department of Breast Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China"
      ],
      "name": "Yueyin Pan"
    },
    {
      "affiliations": [
        "Department of Breast Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China",
        "Department of Medical Oncology, Anhui Provincial Cancer Hospital, Hefei, Anhui, China"
      ],
      "name": "Shoubing Zhou"
    }
  ],
  "title": "Igniting cold tumors: reprogramming the tumor immune microenvironment with dual-payload ADCs in combination with PD-L1&4-1BB bispecific antibodies",
  "uid": "dde71ed3-f562-52b0-956a-d4f92a259509"
}