ArticleCommunications medicine2023
Fusion peptide is superior to co-expressing subunits for arming oncolytic herpes virus with interleukin 12.
Article in Communications medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 5 citations in OpenAlex.
- Preclinical evaluation of triple-mutated oncolytic herpes virus expressing fusion-type interleukin 12 for malignant melanoma.Molecular therapy. Oncology · 2026Article
- Triple-Mutated HSV-1 Expressing Soluble B7-1 Plus CTLA-4 Blockade Suppresses Lymph Node Metastasis in Tongue Cancer.Cancer science · 2026Article
- Induced pluripotent stem cell-derived dendritic cells potentiate the efficacy of interleukin-12-expressing oncolytic HSV-1.Molecular therapy. Oncology · 2026Article
- Advances in Gene Therapy with Oncolytic Viruses and CAR-T Cells and Therapy-Related Groups.Current issues in molecular biology · 2025Review
- Investigating the potential of oncolytic viruses in the treatment of melanoma: where do we go from here?Skin health and disease · 2025Review
- Uncovering the interleukin-12 pharmacokinetic desensitization mechanism and its consequences with mathematical modeling.CPT: pharmacometrics & systems pharmacology · 2025Article
- Optimizing Oncolytic Virotherapy for Malignant Glioma: From Bench to Bedside.Cancer management and research · 2025Review
- Cytokine-armed oncolytic herpes simplex viruses: a game-changer in cancer immunotherapy?Journal for immunotherapy of cancer · 2024Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundG47∆ is a triple-mutated oncolytic herpes simplex virus type 1 (HSV-1) recently approved as a new drug for malignant glioma in Japan. As the next-generation, we develop armed oncolytic HSV-1 using G47∆ as the backbone. Because oncolytic HSV-1 elicits specific antitumor immunity, interleukin 12 (IL-12) can function as an effective payload to enhance the efficacy.
methodsWe evaluate the optimal methods for expressing IL-12 as a payload for G47∆-based oncolytic HSV-1. Two new armed viruses are generated for evaluation by employing different methods to express IL-12: T-mfIL12 expresses murine IL-12 as a fusion peptide, with the genes of two subunits (p35 and p40) linked by bovine elastin motifs, and T-mIL12-IRES co-expresses the subunits, with the two genes separated by an internal ribosome entry site (IRES) sequence.
resultsT-mfIL12 is significantly more efficient in producing IL-12 than T-mIL12-IRES in all cell lines tested, whereas the expression methods do not affect the replication capabilities and cytopathic effects. In two syngeneic mouse subcutaneous tumor models of Neuro2a and TRAMP-C2, T-mfIL12 exhibits a significantly higher efficacy than T-mIL12-IRES when inoculated intratumorally. Furthermore, T-mfIL12 shows a significantly higher intratumoral expression of functional IL-12, causing stronger stimulation of specific antitumor immune responses than T-mIL12-IRES.
conclusionsThe results implicate that a fusion-type expression of IL-12 is a method superior to co-expression of separate subunits, due to higher production of functional IL-12 molecules. This study led to the creation of triple-mutated oncolytic HSV-1 armed with human IL-12 currently used in phase 1/2 trial for malignant melanoma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.