Lindner, Georg and Walter, Annika and Magnus, Clara L. and Rosenhammer, Katharina and Holoborodko, Bohdan and Koch, Victoria and Hirsch, Sarah and Grossmann, Luis and Li, Suqi and Knipe, David M. and Deluca, Neal and Schuler-Thurner, Beatrice and Gross, Stefanie and Schwertner, Barbara and Toelge, Martina and Rohrhofer, Anette and Stoeckl, Sabine and Bauer, Richard J. and Knoll, Gertrud and Ehrenschwender, Martin and Haferkamp, Sebastian and Schmidt, Barbara and Schuster, Philipp (2024) Comparison of the oncolytic activity of a replication-competent and a replication-deficient herpes simplex virus 1. IMMUNOLOGY, 172 (2). pp. 279-294. ISSN 0019-2805, 1365-2567
Full text not available from this repository. (Request a copy)Abstract
In 2015, the oncolytic herpes simplex virus 1 (HSV-1) T-VEC (talimogene laherparepvec) was approved for intratumoral injection in non-resectable malignant melanoma. To determine whether viral replication is required for oncolytic activity, we compared replication-deficient HSV-1 d106S with replication-competent T-VEC. High infectious doses of HSV-1 d106S killed melanoma (n = 10), head-and-neck squamous cell carcinoma (n = 11), and chondrosarcoma cell lines (n = 2) significantly faster than T-VEC as measured by MTT metabolic activity, while low doses of T-VEC were more effective over time. HSV-1 d106S and, to a lesser extent T-VEC, triggered caspase-dependent early apoptosis as shown by pan-caspase inhibition and specific induction of caspases 3/7, 8, and 9. HSV-1 d106S induced a higher ratio of apoptosis-inducing infected cell protein (ICP) 0 to apoptosis-blocking ICP6 than T-VEC. T-VEC was oncolytic for an extended period of time as viral replication continued, which could be partially blocked by the antiviral drug aciclovir. High doses of T-VEC, but not HSV-1 d106S, increased interferon-beta mRNA as part of the intrinsic immune response. When markers of immunogenic cell death were assessed, ATP was released more efficiently in the context of T-VEC than HSV-1 d106S infection, whereas HMGB1 was induced comparatively well. Overall, the early oncolytic effect on three different tumour entities was stronger with the non-replicative strain, while the replication-competent virus elicited a stronger innate immune response and more pronounced immunogenic cell death. Head-to-head comparison of the oncolytic activity of a replication-deficient (HSV-1 d106S) and a replication-competent (T-VEC) herpes virus strain. The former triggered more pronounced and faster apoptosis in 10 melanoma cell lines; the latter was more active over time and induced a more immunogenic cell death. image
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BLOCKS APOPTOSIS; BYSTANDER CELLS; NECROPTOSIS; EXPRESSION; TYPE-1; ACTIVATION; RESPONSES; DEATH; apoptosis; cancer; human; tumour immunology; viral |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Jul 2025 10:16 |
| Last Modified: | 17 Jul 2025 10:16 |
| URI: | https://pred.uni-regensburg.de/id/eprint/63670 |
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