Abstract
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.
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The datasets generated and/or analyzed during the present study are available from the corresponding author on reasonable request.
Code availability
The datasets generated and/or analyzed during the present study are available from the corresponding author on reasonable request.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (No.32301072, No.82504655), the Doctoral Startup Fund Project of North Sichuan Medical College (CBY24-QDA10, CBY22-QDA05, CBY23-QDA14), the Sichuan Science and Technology Program (2026NSFSC0972) and the North Sichuan Medical College Innovation Team (CBYTD-2025A04).
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NZ designed the study and supervised the work, with conceptual support from XJ and SZ. XC, WM and NZ conducted all experiments and analyses and wrote and edited the original draft. JY provided methodological support for the chemotaxis assay of CAR-T cells and contributed to editing the original draft. YG was involved in the design of flow cytometry experiments and in the preparation of the final manuscript. All authors reviewed the manuscript and provided feedback.
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All experimental procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of North Sichuan Medical College (Approval No. 2023043) and were conducted in accordance with the relevant guidelines and regulations of the institution. The collection of peripheral blood samples from healthy donors was performed in compliance with applicable guidelines and regulations and was approved by the Ethics Committee of North Sichuan Medical College (Approval No. 2025004). Written informed consent was obtained from all volunteers who participated in this study.
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Chen, X., Ma, W., Guan, Y. et al. 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. Cell Death Dis (2026). https://doi.org/10.1038/s41419-026-08695-0
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DOI: https://doi.org/10.1038/s41419-026-08695-0
