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<p>Pancreatic ductal adenocarcinoma (PDAC), the primary form of pancreatic cancer, has a very poor prognosis and urgently requires effective treatments. Chimeric antigen receptor T (CAR-T) cell therapy presents a potential treatment approach, yet it is often hindered by several factors, including an immunosuppressive microenvironment, limited tumour infiltration, modest anti-tumour activity and short-term T cell persistence. Here, we engineered an oncolytic herpes simplex virus expressing CXCL-11, IL-12 and a single-chain antibody against PD-1 (named oHSV30) to enhance CAR-T cell infiltration, cytotoxicity and persistence in the tumour microenvironment, thereby improving its therapeutic efficacy. In both immunocompetent and immunodeficient syngeneic PDAC models, we demonstrated that the combination of CAR-T cells with the intratumoural administration of oHSV30 significantly reduced tumour burden and prolonged the survival of tumour-bearing mice. Overall, our data suggest that oHSV30 can be a promising adjuvant for CAR-T therapy in PDAC.</p>

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Arming oncolytic herpes simplex virus with CXCL-11, IL-12 and a single-chain antibody against PD-1 to enhance CAR-T cell therapy in pancreatic ductal adenocarcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月4日

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  • Xixi Chen,
  • Wenbo Ma,
  • Yude Guan,
  • Xiaohan Jin,
  • Jingxuan Yu,
  • Shumin Zhang,
  • Nianchao Zhang

摘要

Pancreatic ductal adenocarcinoma (PDAC), the primary form of pancreatic cancer, has a very poor prognosis and urgently requires effective treatments. Chimeric antigen receptor T (CAR-T) cell therapy presents a potential treatment approach, yet it is often hindered by several factors, including an immunosuppressive microenvironment, limited tumour infiltration, modest anti-tumour activity and short-term T cell persistence. Here, we engineered an oncolytic herpes simplex virus expressing CXCL-11, IL-12 and a single-chain antibody against PD-1 (named oHSV30) to enhance CAR-T cell infiltration, cytotoxicity and persistence in the tumour microenvironment, thereby improving its therapeutic efficacy. In both immunocompetent and immunodeficient syngeneic PDAC models, we demonstrated that the combination of CAR-T cells with the intratumoural administration of oHSV30 significantly reduced tumour burden and prolonged the survival of tumour-bearing mice. Overall, our data suggest that oHSV30 can be a promising adjuvant for CAR-T therapy in PDAC.