{
  "abstract": "Background SCG101 is an autologous T-cell therapy specifically targeting hepatitis B virus (HBV) using a natural, high-affinity T-cell receptor that is stably expressed.Objective We evaluated the safety, pharmacokinetics, pharmacodynamics and efficacy of SCG101 in patients with HBV-related hepatocellular carcinoma (HCC) in an investigator-initiated trial.Design Six human leucocyte antigen (HLA)-A*02:01-positive, serum hepatitis B surface antigen (HBsAg)-positive and hepatitis B e antigen-negative patients with advanced HBV-HCC, who had failed one to three prior systemic therapies, received SCG101 at doses of 5×10 7 or 1×108 TCR-T+ cells/kg three days after lymphodepletion.Results Within 1 week, all patients experienced a significant but transient alanine aminotransferase elevation paralleled by a 76±57 fold expansion of T cells detected in peripheral blood. No neurotoxicity, but a cytokine release syndrome reaching up to grade 3 was observed. However, these side effects were not dose-limiting and could be managed with corticosteroids, anti-interleukin-6 and/or vasopressor therapy. Indicating on-target activity of SCG101, serum HBsAg levels dropped by 1.96 (0.16–3.84) log 10 within 2 weeks. According to modified Response Evaluation Criteria in Solid Tumours, three of the six patients achieved tumour shrinkage with a best percentage change in target lesion size of −19.5%, −74.6% and −100%. One showed complete remission of the target lesion, remaining progression-free for 27 months and one other achieved a durable (>6 months) remission. During follow-up (median 10.9 months), three patients died, and one was lost to follow-up.Conclusion As monotherapy for patients with HBV-HCC, SCG101 demonstrated pronounced antiviral and antitumour activities and a safety profile manageable with supportive care. SCG101’s T-cell expansion, serum HBsAg drop and tumour response collectively underscore on-target activity.Trial registration number NCT05339321.",
  "authors": [
    {
      "affiliations": [
        "Department of Liver Surgery, Peking Union Medical College Hospital, Beijing, Beijing, China"
      ],
      "name": "Xiang'an Wu"
    },
    {
      "affiliations": [
        "Department of General Surgery, The Sixth People’s Hospital of Shenyang, Shenyang, China"
      ],
      "name": "Dongmei Quan"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Zhongshan Hospital Fudan University, Shanghai, Shanghai, China"
      ],
      "name": "Wei Li"
    },
    {
      "affiliations": [
        "SCG Cell Therapy GmbH, Munich, Germany"
      ],
      "name": "Karin Wisskirchen"
    },
    {
      "affiliations": [
        "Department of General Surgery, The Sixth People’s Hospital of Shenyang, Shenyang, China"
      ],
      "name": "Wei Wu"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Zhongshan Hospital Fudan University, Shanghai, Shanghai, China"
      ],
      "name": "Yuhong Zhou"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China"
      ],
      "name": "Yun-Peng Liu"
    },
    {
      "affiliations": [
        "Department of Liver Surgery, Peking Union Medical College Hospital, Beijing, Beijing, China"
      ],
      "name": "Xueshuai Wan"
    },
    {
      "affiliations": [
        "SCG Cell Therapy Pte Ltd, Singapore"
      ],
      "name": "Xiaorui Wang"
    },
    {
      "affiliations": [
        "SCG (Shanghai) Cell Therapy Co Ltd, Shanghai, China"
      ],
      "name": "Xuxu Zhang"
    },
    {
      "affiliations": [
        "SCG (Shanghai) Cell Therapy Co Ltd, Shanghai, China"
      ],
      "name": "Lu Yang"
    },
    {
      "affiliations": [
        "SCG (Shanghai) Cell Therapy Co Ltd, Shanghai, China"
      ],
      "name": "Mengyao Zheng"
    },
    {
      "affiliations": [
        "SCG Cell Therapy Pte Ltd, Singapore"
      ],
      "name": "Ke Zhang"
    },
    {
      "affiliations": [
        "Institute of Virology, Technical University of Munich / Helmholtz Munich, Munich, Germany",
        "German Center for Infection Research, Munich, Germany"
      ],
      "name": "Ulrike Protzer"
    },
    {
      "affiliations": [
        "Department of Liver Surgery, Peking Union Medical College Hospital, Beijing, Beijing, China"
      ],
      "name": "Shunda Du"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China"
      ],
      "name": "Xiujuan Qu"
    }
  ],
  "title": "Clinical results of an HBV-specific T-cell receptor-T-cell therapy (SCG101) in patients with HBV-related hepatocellular carcinoma treated in an investigator-initiated, interventional trial",
  "uid": "04abf907-9e13-563d-8959-e68d84388651"
}