Comparison of the oncolytic activity of a replication-competent and a replication-deficient herpes simplex virus 1

Lindner G, Walter A, Magnus CL, Rosenhammer K, Holoborodko B, Koch V, Hirsch S, Grossmann L, Li S, Knipe DM, DeLuca N, Schuler-Thurner B, Gross S, Schwertner B, Toelge M, Rohrhofer A, Stöckl S, Bauer RJ, Knoll G, Ehrenschwender M, Haferkamp S, Schmidt B, Schuster P (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Immunology Wiley-Blackwell

DOI: 10.1111/imm.13775

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-β 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.

Authors with CRIS profile

Beatrice Schuler-Thurner Medizinische Fakultät

Involved external institutions

Universitätsklinikum Regensburg DE Germany (DE) Universität Regensburg DE Germany (DE) Veterans Affairs Healthcare System Boston and Harvard Medical School US United States (USA) (US) University of Pittsburgh US United States (USA) (US)

How to cite

APA:

Lindner, G., Walter, A., Magnus, C.L., Rosenhammer, K., Holoborodko, B., Koch, V.,... Schuster, P. (2024). Comparison of the oncolytic activity of a replication-competent and a replication-deficient herpes simplex virus 1. Immunology. https://doi.org/10.1111/imm.13775

MLA:

Lindner, Georg, et al. "Comparison of the oncolytic activity of a replication-competent and a replication-deficient herpes simplex virus 1." Immunology (2024).

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