{
  "abstract": "Background Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy with limited treatment options and poor prognosis, especially for patients who failed standard therapies.Objective To explore the safety, efficacy and immunological mechanisms of the novel edition of oncolytic virus vaccination, VG161, a multiarmed oncolytic herpes simplex virus-1 expressing interleukin (IL)-12, IL-15 and a programmed death-ligand 1 antagonist, in patients with advanced ICC.Design This pooled analysis integrates data from two multicentre clinical studies: a Phase I dose-escalation study and a Phase IIa exploratory study. 24 patients with advanced ICC received ultrasound-guided intratumoral injections of VG161. Multiomics analyses were performed on longitudinal tumour biopsies to evaluate immune modulation.Results The oncolytic virus therapy VG161 was well tolerated and showed encouraging antitumour activity, including improved overall survival versus second-line FOLFOX chemotherapy, even though most patients received VG161 as third-line or later therapy. Notably, patients previously treated with immune checkpoint inhibitors (CPIs) experienced enhanced benefit. Multiomics profiling of longitudinal biopsies revealed significant remodelling of the immunosuppressive tumour microenvironment, with proliferated infiltration of antigen-presenting cells, CD8 + T cell activation and M2-like macrophage depletion. Single-cell and spatial transcriptomics identified epithelial and macrophage subpopulations (Epi-C2 and Macro-C1QC) as potential biomarkers of response and resistance.Conclusion These early-phase findings suggest that VG161 elicits meaningful immune activation in ICC and supports further investigation. By inducing both direct oncolysis and multilayered immune activation, VG161 shows clinical benefit in a heavily pretreated population and holds promise for integration with CPI-based regimens. Validation in larger trials is warranted.",
  "authors": [
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China",
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China"
      ],
      "name": "Yinan Shen"
    },
    {
      "affiliations": [
        "Department of Ultrasound Medicine, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Xinyan Jin"
    },
    {
      "affiliations": [
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China"
      ],
      "name": "Wei Song"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Tian Fang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China",
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China"
      ],
      "name": "Yuwei Li"
    },
    {
      "affiliations": [
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China"
      ],
      "name": "Zeda Zhao"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Xingmei Liang"
    },
    {
      "affiliations": [
        "Shanghai Virogin Biotech, Shanghai, China"
      ],
      "name": "Qian Tan"
    },
    {
      "affiliations": [
        "Shanghai Virogin Biotech, Shanghai, China"
      ],
      "name": "Ronghua Zhao"
    },
    {
      "affiliations": [
        "China National Biotec Group, Shanghai, China",
        "CNBG-Virogin Biotech Shanghai, Shanghai, Shanghai, China"
      ],
      "name": "Yuntao Zhang"
    },
    {
      "affiliations": [
        "Shanghai Virogin Biotech, Shanghai, China",
        "CNBG-Virogin Biotech Shanghai, Shanghai, Shanghai, China"
      ],
      "name": "William Jia"
    },
    {
      "affiliations": [
        "Shanghai Virogin Biotech, Shanghai, China",
        "CNBG-Virogin Biotech Shanghai, Shanghai, Shanghai, China"
      ],
      "name": "Hongwei Huang"
    },
    {
      "affiliations": [
        "CNBG-Virogin Biotech Shanghai, Shanghai, Shanghai, China"
      ],
      "name": "Tengjie Wu"
    },
    {
      "affiliations": [
        "Zhongshan Hospital Fudan University, Shanghai, China"
      ],
      "name": "Guoming Shi"
    },
    {
      "affiliations": [
        "Department of Radiology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China"
      ],
      "name": "Zhewei Zhang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, Nanchang University Second Affiliated Hospital, Nanchang, Jiangxi, China"
      ],
      "name": "Enliang Li"
    },
    {
      "affiliations": [
        "Department of Ultrasound Medicine, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Guyue Wei"
    },
    {
      "affiliations": [
        "Department of Ultrasound Medicine, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Tao Jiang"
    },
    {
      "affiliations": [
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China"
      ],
      "name": "Zijun Wang"
    },
    {
      "affiliations": [
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China"
      ],
      "name": "Zifan Yang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China",
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China"
      ],
      "name": "Danni Lin"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China",
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China"
      ],
      "name": "Linghao Xia"
    },
    {
      "affiliations": [
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China"
      ],
      "name": "Sida Guo"
    },
    {
      "affiliations": [
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China"
      ],
      "name": "Jiaxin Li"
    },
    {
      "affiliations": [
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China"
      ],
      "name": "Fang Wei"
    },
    {
      "affiliations": [
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China"
      ],
      "name": "Xueyan Shi"
    },
    {
      "affiliations": [
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China"
      ],
      "name": "Siyuan Chen"
    },
    {
      "affiliations": [
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China"
      ],
      "name": "Chuntian Tu"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China",
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China"
      ],
      "name": "Zhanyi Shou"
    },
    {
      "affiliations": [
        "CNBG-Virogin Biotech Shanghai, Shanghai, Shanghai, China"
      ],
      "name": "Longshen Xie"
    },
    {
      "affiliations": [
        "CNBG-Virogin Biotech Shanghai, Shanghai, Shanghai, China"
      ],
      "name": "Hongchao Zhang"
    },
    {
      "affiliations": [
        "CNBG-Virogin Biotech Shanghai, Shanghai, Shanghai, China"
      ],
      "name": "Hangyu Zhou"
    },
    {
      "affiliations": [
        "CNBG-Virogin Biotech Shanghai, Shanghai, Shanghai, China"
      ],
      "name": "Peilin Lan"
    },
    {
      "affiliations": [
        "Shanghai Virogin Biotech, Shanghai, China",
        "CNBG-Virogin Biotech Shanghai, Shanghai, Shanghai, China"
      ],
      "name": "Jun Ding"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Wei Chen"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Yufu Ye"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China",
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China"
      ],
      "name": "Xiaozhen Zhang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China",
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China"
      ],
      "name": "Yiwen Chen"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China",
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China"
      ],
      "name": "Xiang Li"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Zhenglong Zhai"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Wendi Hu"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China",
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China"
      ],
      "name": "Xiaoyu Zhang"
    },
    {
      "affiliations": [
        "Department of Radiotherapy, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Lei Wang"
    },
    {
      "affiliations": [
        "Department of Radiotherapy, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Xiaoli Sun"
    },
    {
      "affiliations": [
        "Department of Clinical Pharmacy, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Qingwei Zhao"
    },
    {
      "affiliations": [
        "Department of Clinical Pharmacy, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Xingjiang Hu"
    },
    {
      "affiliations": [
        "Department of Clinical Pharmacy, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Youlei Wang"
    },
    {
      "affiliations": [
        "Department of Clinical Pharmacy, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Zhuojun Zhou"
    },
    {
      "affiliations": [
        "Department of Clinical Pharmacy, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Jiejing Kai"
    },
    {
      "affiliations": [
        "Department of Clinical Pharmacy, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Jichen Li"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China"
      ],
      "name": "Wei Zhang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China",
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China"
      ],
      "name": "Xueli Bai"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China",
        "Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China"
      ],
      "name": "Tingbo Liang"
    }
  ],
  "title": "Hypothesis-generating evaluation of multi-armoured oncolytic HSV-1 (VG161) in intrahepatic cholangiocarcinoma: pooled insights from multicentre studies",
  "uid": "c42b7462-67fa-533c-a33d-b555512f55a5"
}