Current status of clinical trials assessing oncolytic virus therapy for urological cancers

Taguchi, Satoru; Fukuhara, Hiroshi; Homma, Yukio; Todo, Tomoki

doi:10.1111/iju.13325

Cited by 45 publications

(34 citation statements)

References 97 publications

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“…At preclinical level, it has been shown that oncolytic adenoviruses are successful in treating MIBC [37]. Several other oncolytic viruses have shown efficacy in urothelial carcinomas and some are currently tested in clinical trials [38]. Combination of oncolytic viruses with immune checkpoint inhibitors and targeted therapies has been proven to be a successful strategy to enhance the efficiency of therapy response to oncolytic virus [39,40].…”

Section: Introductionmentioning

confidence: 99%

STAT3/5 Inhibitors Suppress Proliferation in Bladder Cancer and Enhance Oncolytic Adenovirus Therapy

Hindupur

Schmid

Koch

et al. 2020

IJMS

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The JAK-STAT signalling pathway regulates cellular processes like cell division, cell death and immune regulation. Dysregulation has been identified in solid tumours and STAT3 activation is a marker for poor outcome. The aim of this study was to explore potential therapeutic strategies by targeting this pathway in bladder cancer (BC). High STAT3 expression was detected in 51.3% from 149 patient specimens with invasive bladder cancer by immunohistochemistry. Protein expression of JAK, STAT and downstream targets were confirmed in 10 cell lines. Effects of the JAK inhibitors Ruxolitinib and BSK-805, and STAT3/5 inhibitors Stattic, Nifuroxazide and SH-4-54 were analysed by cell viability assays, immunoblotting, apoptosis and cell cycle progression. Treatment with STAT3/5 but not JAK1/2 inhibitors reduced survival, levels of phosphorylated STAT3 and Cyclin-D1 and increased apoptosis. Tumour xenografts, using the chicken chorioallantoic membrane (CAM) model responded to Stattic monotherapy. Combination of Stattic with Cisplatin, Docetaxel, Gemcitabine, Paclitaxel and CDK4/6 inhibitors showed additive effects. The combination of Stattic with the oncolytic adenovirus XVir-N-31 increased viral replication and cell lysis. Our results provide evidence that inhibitors against STAT3/5 are promising as novel mono- and combination therapy in bladder cancer.

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Section: Introductionmentioning

confidence: 99%

STAT3/5 Inhibitors Suppress Proliferation in Bladder Cancer and Enhance Oncolytic Adenovirus Therapy

Hindupur

Schmid

Koch

et al. 2020

IJMS

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“…13 Recently, oncolytic adenoviruses have been commonly used in clinical trials for cancer gene therapy. 14,15 Among them, the cancer-targeting gene virotherapy (CTGVT) strategy 16 might be a useful strategy for the treatment of advanced or metastatic cancer. For example, inserting the vascular endothelial cell growth inhibitor (VEGI) into a selectively replicating adenovirus with an E1B-55kDa gene deletion (ZD55) to construct ZD55-VEGI-251 leads to a much more severe cytopathic effect than control viruses on human cancer cell line HeLa, hepatoma cell line SMMC-7721, and CRC cell line SW620.…”

Section: Introductionmentioning

confidence: 99%

A Triple-Regulated Oncolytic Adenovirus Carrying MicroRNA-143 Exhibits Potent Antitumor Efficacy in Colorectal Cancer

Luo

Song

Deng

et al. 2020

Molecular Therapy - Oncolytics

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The cancer-targeting gene virotherapy might be a useful strategy for the treatment of cancer, because it could combine the advantages of both gene therapy and virotherapy. This study aimed to construct a triple-regulated oncolytic adenovirus, Ad-RGD-Survivin-ZD55-miR-143, carrying the therapeutic gene miR-143 and evaluate its possible antitumor effect in colorectal cancer. We observed that miR-143 was lowly expressed in patients with colorectal cancer. The upregulation of miR-143 could inhibit cell proliferation and induce cell apoptosis by targeting KRAS in colorectal cancer cells. Then, Ad-RGD-Survivin-ZD55-miR-143 was successfully constructed in this study. Cells infected with Ad-RGD-Survivin-ZD55-miR-143 could inhibit cell proliferation, suppress cell migration and invasion, arrest cells at the G1 phase, and induce cellular apoptosis. At the same time, Ad-RGD-Survivin-ZD55-miR-143 decreased the expression of PARP-1 and KRAS protein in vitro. In a HCT116 xenograft model, intratumoral injection of Ad-RGD-Survivin-ZD55-miR-143 resulted in reduced tumor growth. Furthermore, Ad-RGD-Survivin-ZD55-miR-143 induced apoptosis and decreased the expression level of KRAS in HCT116 xenograft cells. Our results suggested that Ad-RGD-Survivin-ZD55-miR-143 produced a strong antitumor effect by targeting KRAS and that this strategy could broaden the therapeutic options for treating colorectal cancer.

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“…Moreover, the OV Talimogene Laherparepvec (Imlygic ® , T‐VEC) has recently been licensed in the United States and Europe for the treatment of melanoma . In the few early‐phase clinical trials that have included PCa patients, safety and efficacy data were also encouraging . However, most of the OVs currently under development need to be applied intratumorally, as pre‐existing or rapidly induced neutralizing antiviral antibodies limit the systemic delivery to the tumor tissue and thereby the efficacy in metastatic disease.…”

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confidence: 99%

“…7,8 In the few earlyphase clinical trials that have included PCa patients, safety and efficacy data were also encouraging. 9 However, most of the OVs currently under development need to be applied intratumorally, as pre-existing or rapidly induced neutralizing antiviral antibodies limit the systemic delivery to the tumor tissue and thereby the efficacy in metastatic disease. Among the OVs currently in the development pipeline, vesicular stomatitis virus (VSV) carrying the envelope protein (GP) of the lymphocytic choriomeningitis virus, VSV-GP, has several outstanding features: (i) There is practically no pre-existing immunity against VSV-GP in the general population and VSV-GP does not readily induce neutralizing antibodies.…”

mentioning

confidence: 99%

Oncolytic activity of the rhabdovirus VSV‐GP against prostate cancer

Urbiola

Santer

Petersson

et al. 2018

Intl Journal of Cancer

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Oncolytic viruses, including the oncolytic rhabdovirus VSV-GP tested here, selectively infect and kill cancer cells and are a promising new therapeutic modality. Our aim was to study the efficacy of VSV-GP, a vesicular stomatitis virus carrying the glycoprotein of lymphocytic choriomeningitis virus, against prostate cancer, for which current treatment options still fail to cure metastatic disease. VSV-GP was found to infect 6 of 7 prostate cancer cell lines with great efficacy. However, susceptibility was reduced in one cell line with low virus receptor expression and in 3 cell lines after interferon alpha treatment. Four cell lines had developed resistance to interferon type I at different levels of the interferon signaling pathway, resulting in a deficient antiviral response. In prostate cancer mouse models, long-term remission was achieved upon intratumoral and, remarkably, also upon intravenous treatment of subcutaneous tumors and bone metastases. These promising efficacy data demonstrate that treatment of prostate cancer with VSV-GP is feasible and safe in preclinical models and encourage further preclinical and clinical development of VSV-GP for systemic treatment of metastatic prostate cancer.

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Current status of clinical trials assessing oncolytic virus therapy for urological cancers

Abstract: Oncolytic virus therapy has recently been recognized as a promising new option for cancer treatment. Oncolytic viruses replicate selectively in cancer cells,

Cited by 45 publications

References 97 publications

STAT3/5 Inhibitors Suppress Proliferation in Bladder Cancer and Enhance Oncolytic Adenovirus Therapy

STAT3/5 Inhibitors Suppress Proliferation in Bladder Cancer and Enhance Oncolytic Adenovirus Therapy

A Triple-Regulated Oncolytic Adenovirus Carrying MicroRNA-143 Exhibits Potent Antitumor Efficacy in Colorectal Cancer

Oncolytic activity of the rhabdovirus VSV‐GP against prostate cancer

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