Neoadjuvant use of oncolytic herpes virus G47Δ prevents local recurrence after insufficient resection in tongue cancer models
A complete resection of tongue cancer is often difficult. We investigate the usefulness of administering G47Δ (teserpaturev), a triple-mutated oncolytic herpes simplex virus type 1, prior to resection. G47Δ exhibits good cytopathic effects and replication capabilities in all head and neck cancer cel...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Molecular Therapy: Oncolytics |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2372770523000487 |
| _version_ | 1797745979156332544 |
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| author | Kosuke Inoue Hirotaka Ito Miwako Iwai Minoru Tanaka Yoshiyuki Mori Tomoki Todo |
| author_facet | Kosuke Inoue Hirotaka Ito Miwako Iwai Minoru Tanaka Yoshiyuki Mori Tomoki Todo |
| author_sort | Kosuke Inoue |
| collection | DOAJ |
| description | A complete resection of tongue cancer is often difficult. We investigate the usefulness of administering G47Δ (teserpaturev), a triple-mutated oncolytic herpes simplex virus type 1, prior to resection. G47Δ exhibits good cytopathic effects and replication capabilities in all head and neck cancer cell lines tested. In an orthotopic SCCVII tongue cancer model of C3H/He mice, an intratumoral inoculation with G47Δ significantly prolongs the survival. Further, mice with orthotopic tongue cancer received neoadjuvant G47Δ (or mock) therapy with or without “hemilateral” resection, the maximum extent avoiding surgical deaths. Neoadjuvant G47Δ and resection led to 10/10 survival (120 days), whereas the survivals for G47Δ alone and resection alone were 6/10 and 5/10, respectively: all control animals died by day 11. Furthermore, 100% survival was achieved with neoadjuvant G47Δ therapy even when the resection area was narrowed to “partial,” providing insufficient resection margins, whereas hemilateral resection alone caused death by local recurrence in half of the animals. G47Δ therapy caused increased number of tumor-infiltrating CD8+ and CD4+ cells, increased F4/80+ cells within the residual tongues, and increased expression of immune-related genes in and around the tumor. These results imply that neoadjuvant use of G47Δ is useful for preventing local recurrence after tongue cancer surgery. |
| first_indexed | 2024-03-12T15:30:34Z |
| format | Article |
| id | doaj.art-73dc09e45e8749bba30f440dcc0e4402 |
| institution | Directory Open Access Journal |
| issn | 2372-7705 |
| language | English |
| last_indexed | 2024-03-12T15:30:34Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncolytics |
| spelling | doaj.art-73dc09e45e8749bba30f440dcc0e44022023-08-10T04:34:39ZengElsevierMolecular Therapy: Oncolytics2372-77052023-09-01307285Neoadjuvant use of oncolytic herpes virus G47Δ prevents local recurrence after insufficient resection in tongue cancer modelsKosuke Inoue0Hirotaka Ito1Miwako Iwai2Minoru Tanaka3Yoshiyuki Mori4Tomoki Todo5Division of Innovative Cancer Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Department of Oral and Maxillofacial Surgery, Jichi Medical University Hospital, Tochigi 329-0498, JapanDivision of Innovative Cancer Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, JapanDivision of Innovative Cancer Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, JapanDivision of Innovative Cancer Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Project Division of Oncolytic Virus Development, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, JapanDepartment of Oral and Maxillofacial Surgery, Jichi Medical University Hospital, Tochigi 329-0498, JapanDivision of Innovative Cancer Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Corresponding author: Tomoki Todo, Division of Innovative Cancer Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.A complete resection of tongue cancer is often difficult. We investigate the usefulness of administering G47Δ (teserpaturev), a triple-mutated oncolytic herpes simplex virus type 1, prior to resection. G47Δ exhibits good cytopathic effects and replication capabilities in all head and neck cancer cell lines tested. In an orthotopic SCCVII tongue cancer model of C3H/He mice, an intratumoral inoculation with G47Δ significantly prolongs the survival. Further, mice with orthotopic tongue cancer received neoadjuvant G47Δ (or mock) therapy with or without “hemilateral” resection, the maximum extent avoiding surgical deaths. Neoadjuvant G47Δ and resection led to 10/10 survival (120 days), whereas the survivals for G47Δ alone and resection alone were 6/10 and 5/10, respectively: all control animals died by day 11. Furthermore, 100% survival was achieved with neoadjuvant G47Δ therapy even when the resection area was narrowed to “partial,” providing insufficient resection margins, whereas hemilateral resection alone caused death by local recurrence in half of the animals. G47Δ therapy caused increased number of tumor-infiltrating CD8+ and CD4+ cells, increased F4/80+ cells within the residual tongues, and increased expression of immune-related genes in and around the tumor. These results imply that neoadjuvant use of G47Δ is useful for preventing local recurrence after tongue cancer surgery.http://www.sciencedirect.com/science/article/pii/S2372770523000487tongue cancerG47Δoncolytic virus therapyimmunotherapyneoadjuvant therapylocal recurrence |
| spellingShingle | Kosuke Inoue Hirotaka Ito Miwako Iwai Minoru Tanaka Yoshiyuki Mori Tomoki Todo Neoadjuvant use of oncolytic herpes virus G47Δ prevents local recurrence after insufficient resection in tongue cancer models Molecular Therapy: Oncolytics tongue cancer G47Δ oncolytic virus therapy immunotherapy neoadjuvant therapy local recurrence |
| title | Neoadjuvant use of oncolytic herpes virus G47Δ prevents local recurrence after insufficient resection in tongue cancer models |
| title_full | Neoadjuvant use of oncolytic herpes virus G47Δ prevents local recurrence after insufficient resection in tongue cancer models |
| title_fullStr | Neoadjuvant use of oncolytic herpes virus G47Δ prevents local recurrence after insufficient resection in tongue cancer models |
| title_full_unstemmed | Neoadjuvant use of oncolytic herpes virus G47Δ prevents local recurrence after insufficient resection in tongue cancer models |
| title_short | Neoadjuvant use of oncolytic herpes virus G47Δ prevents local recurrence after insufficient resection in tongue cancer models |
| title_sort | neoadjuvant use of oncolytic herpes virus g47δ prevents local recurrence after insufficient resection in tongue cancer models |
| topic | tongue cancer G47Δ oncolytic virus therapy immunotherapy neoadjuvant therapy local recurrence |
| url | http://www.sciencedirect.com/science/article/pii/S2372770523000487 |
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