{"doi":"10.1111/imm.13775","title":"Comparison of the oncolytic activity of a replication‐competent and a replication‐deficient herpes simplex virus 1","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.","journal":"Immunology","year":2024,"id":461922,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9628,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1291389,"name":"Annika Walter","orcid":null,"position":1,"is_corresponding":false},{"id":1291390,"name":"Clara Luzia Magnus","orcid":null,"position":2,"is_corresponding":false},{"id":1291391,"name":"Katharina Rosenhammer","orcid":null,"position":3,"is_corresponding":false},{"id":1291392,"name":"Bohdan Holoborodko","orcid":null,"position":4,"is_corresponding":false},{"id":810791,"name":"Victoria Koch","orcid":null,"position":5,"is_corresponding":false},{"id":1291393,"name":"Sarah Hirsch","orcid":null,"position":6,"is_corresponding":false},{"id":1291394,"name":"Luis Grossmann","orcid":null,"position":7,"is_corresponding":false},{"id":1291395,"name":"Suqi Li","orcid":null,"position":8,"is_corresponding":false},{"id":392218,"name":"David M. 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