Efficacy and safety of a third-generation oncolytic herpes virus G47Δ in models of human esophageal carcinoma

Yajima, Shoh; Sugawara, Katsuhiko; Iwai, Miwako; Tanaka, Minoru; Seto, Yasuyuki; Todo, Tomoki

doi:10.1016/j.omto.2021.10.012

Cited by 20 publications

(20 citation statements)

References 56 publications

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“…To date, G47Δ has been shown to be efficacious via the same mechanism of action in various solid tumors in vivo, including prostate cancer, gastric cancer, hepatocellular carcinoma, tongue cancer, esophageal cancer, breast cancer, neuroblastoma and malignant peripheral nerve sheath tumor 2,3,[35][36][37][38][39][40][41] . Oncolytic HSV-1, including G47∆, does not infect normal bone marrow-derived cells 2,42 , but recent studies show that even some blood cancers are susceptible to G47∆ (refs.…”

Section: Discussionmentioning

confidence: 99%

Intratumoral oncolytic herpes virus G47∆ for residual or recurrent glioblastoma: a phase 2 trial

Todo

Ito

Ino

et al. 2022

Nat Med

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220

157

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This investigator-initiated, phase 2, single-arm trial primarily assessed the efficacy of G47∆, a triple-mutated, third-generation oncolytic herpes simplex virus type 1, in 19 adult patients with residual or recurrent, supratentorial glioblastoma after radiation therapy and temozolomide (UMIN-CTR Clinical Trial Registry UMIN000015995). G47Δ was administered intratumorally and repeatedly for up to six doses. The primary endpoint of 1-yr survival rate after G47∆ initiation was 84.2% (95% confidence interval, 60.4–96.6; 16 of 19). The prespecified endpoint was met and the trial was terminated early. Regarding secondary endpoints, the median overall survival was 20.2 (16.8–23.6) months after G47∆ initiation and 28.8 (20.1–37.5) months from the initial surgery. The most common G47∆-related adverse event was fever (17 of 19) followed by vomiting, nausea, lymphocytopenia and leukopenia. On magnetic resonance imaging, enlargement of and contrast-enhancement clearing within the target lesion repeatedly occurred after each G47∆ administration, which was characteristic to this therapy. Thus, the best overall response in 2 yr was partial response in one patient and stable disease in 18 patients. Biopsies revealed increasing numbers of tumor-infiltrating CD4+/CD8+ lymphocytes and persistent low numbers of Foxp3+ cells. This study showed a survival benefit and good safety profile, which led to the approval of G47∆ as the first oncolytic virus product in Japan.

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Section: Discussionmentioning

confidence: 99%

Intratumoral oncolytic herpes virus G47∆ for residual or recurrent glioblastoma: a phase 2 trial

Todo

Ito

Ino

et al. 2022

Nat Med

Self Cite

220

157

View full text Add to dashboard Cite

show abstract

“…G47d administered intratumorally has been found to have an effective oncolytic effect on subcutaneous and in-situ EC tumors in mice. Furthermore, g47d was safe when given orally and intraesophageally in high doses (Yajima et al, 2021). In a tumorbearing animal model, VSV reduces the development of a variety of cancers when administered intratumorally or intravenously , indicating that it might be used to treat esophageal cancer.…”

Section: Esophageal Cancermentioning

confidence: 95%

“…Thus, IFN treatment antagonizes the M1 virus's oncolytic action. Other anti-hepatitis drugs, such as Reduced toxicity to pancreas (Yajima et al, 2021) direct anti-viral small molecule drugs (DAA) and ribavirin (RBV) for chronic hepatitis C, do not inhibit M1's oncolytic activity. As a result, the patient's conditions must be evaluated before beginning IFNa and M1 virus combined therapy in patients with hepatocellular carcinoma complicated by hepatitis B virus or hepatitis B virus infection.…”

Section: Liver Cancermentioning

confidence: 99%

Oncolytic Viruses: Immunotherapy Drugs for Gastrointestinal Malignant Tumors

Oduro

Guo

et al. 2022

Front. Cell. Infect. Microbiol.

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Oncolytic virus therapy has advanced rapidly in recent years. Natural or transgenic viruses can target tumor cells and inhibit tumor growth and metastasis in various ways without interfering with normal cell and tissue function. Oncolytic viruses have a high level of specificity and are relatively safe. Malignant tumors in the digestive system continue to have a high incidence and mortality rate. Although existing treatment methods have achieved some curative effects, they still require further improvement due to side effects and a lack of specificity. Many studies have shown that oncolytic viruses can kill various tumor cells, including malignant tumors in the digestive system. This review discusses how oncolytic virus therapy improves malignant tumors in the digestive system from the point-of-view of basic and clinical studies. Also, the oncolytic virus anti-tumor mechanisms underpinning the therapeutic potential of oncolytic viruses are expounded. In all, we argue that oncolytic viruses might eventually provide therapeutic solutions to malignant tumors in the digestive system.

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“…G47Δ (teserpaturev) is a triple-mutated, third-generation oncolytic HSV-1, noted for its markedly enhanced antitumor activity in vivo . 3 G47Δ is found effective for a variety of cancers, 4 , 5 , 6 , 7 , 8 , 9 , 10 and it has been tested in patients with glioblastoma, 11 prostate cancer, olfactory neuroblastoma, and malignant mesothelioma. Based on the results of the phase II study, G47Δ was recently approved as a new drug for malignant glioma in Japan.…”

Section: Introductionmentioning

confidence: 99%

Overcoming resistance of stroma-rich pancreatic cancer with focal adhesion kinase inhibitor combined with G47Δ and immune checkpoint inhibitors

Yamada¹,

Tateishi²,

Iwai³

et al. 2023

Molecular Therapy - Oncolytics

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Efficacy and safety of a third-generation oncolytic herpes virus G47Δ in models of human esophageal carcinoma

Cited by 20 publications

References 56 publications

Intratumoral oncolytic herpes virus G47∆ for residual or recurrent glioblastoma: a phase 2 trial

Intratumoral oncolytic herpes virus G47∆ for residual or recurrent glioblastoma: a phase 2 trial

Oncolytic Viruses: Immunotherapy Drugs for Gastrointestinal Malignant Tumors

Overcoming resistance of stroma-rich pancreatic cancer with focal adhesion kinase inhibitor combined with G47Δ and immune checkpoint inhibitors

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