A dopamine antagonist, domperidone enhances the replication of an oncolytic adenovirus in human tumour cells

Nishimae, Fumitaka; Sakurai, Fuminori; Ono, Ryosuke; Onishi, Rika; Takayama, Kosuke; Mizuguchi, Hiroyuki

doi:10.1099/jgv.0.001752

Cited by 2 publications

(2 citation statements)

References 23 publications

(34 reference statements)

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“…1 ). OAd-tAIB-Luc has the human telomerase reverse transcriptase (hTERT) promoter-driven E1A gene linked with the E1B gene by the internal ribosome entry site (tAIB) and the cytomegalovirus (CMV) promoter-driven luciferase gene cassette 25 . The previous study demonstrated that OAd containing the same E1 gene expression cassette mediates no apparent cytotoxicity in normal cells 26 .…”

Section: Resultsmentioning

confidence: 99%

“…The CMV promoter-driven firefly luciferase-expressing replication-incompetent Ad5 vector, Ad-L2, was previously produced 48 . The recombinant OAd5 expressing an hTERT promoter-driven Ad5 E1 gene and CMV promoter-driven firefly luciferase gene (OAd-tAIB-Luc) was previously constructed 25 . The determination of virus particle (VP) titers was accomplished according to Maizel et al 49 In vitro luciferase assay.…”

Section: Methodsmentioning

confidence: 99%

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Effects of pre-existing anti-adenovirus antibodies on transgene expression levels and therapeutic efficacies of arming oncolytic adenovirus

Ono

Nishimae

Wakida

et al. 2022

Sci Rep

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Oncolytic adenoviruses (OAds), most of which are based on species C human adenovirus serotype 5 (Ad5) (OAd5), have recently received much attention as potential anticancer agents. High seroprevalence of anti-Ad5 neutralizing antibodies is a major hurdle for Ad5-based gene therapy. However, the impacts of anti-Ad5 neutralizing antibodies on OAd5-mediated transgene expression in the tumor and antitumor effects remain to be fully elucidated. In this study, we examined the impact of anti-Ad5 neutralizing antibodies on the OAd5-mediated antitumor effects and OAd5-mediated transgene expression. The luciferase expression of OAd-tAIB-Luc, which contains the cytomegalovirus promoter-driven luciferase gene, was inhibited in human cultured cells in the presence of human serum. Although the inhibitory effects of human serum possessing the low anti-Ad5 neutralizing antibody titers were overcome by long-term infection, the in vitro tumor cell lysis activities of OAd-tAIB-Luc were entirely attenuated by human serum containing the high titers of anti-Ad5 neutralizing antibodies. OAd-tAIB-Luc-mediated luciferase expression in the subcutaneous tumors 3 days after administration and tumor growth suppression levels following intratumoral administration were significantly lower in mice possessing the high titers of anti-Ad5 neutralizing antibodies, compared to those in control mice. These results suggested that pre-existing anti-Ad5 antibodies attenuated both transgene expression and potential antitumor effects of OAd5 following intratumoral administration.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Effects of pre-existing anti-adenovirus antibodies on transgene expression levels and therapeutic efficacies of arming oncolytic adenovirus

Ono

Nishimae

Wakida

et al. 2022

Sci Rep

Self Cite

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Oncolytic adenoviruses and the treatment of pancreatic cancer: a review of clinical trials

Taylor

Lopez

2023

J Cancer Res Clin Oncol

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Purpose Pancreatic ductal adenocarcinoma (PDAC) remains a common and difficult cancer to treat. Surgical resection and chemotherapy are standard of care and clinical outcomes remain poor. Oncolytic adenoviruses are a unique approach to the treatment of this challenging cancer, aiming to overcome the features of this disease that pose the key obstacles to standard therapies. This paper provides a detailed review of the clinical trials of conditionally-replicative adenoviruses in pancreatic cancer to date, with a brief summary of the past preclinical literature and future prospects of this therapy. Methods MEDLINE, Embase, and clinicaltrials.gov were searched from inception to December 23rd 2022 for clinical trials of conditionally-replicative adenoviruses used in patients with pancreatic ductal adenocarcinoma. Primary features for review included patient demographics, treatment protocol including dose and administration route, adverse events, patient responses and survival rates. Results The six published clinical trials suggest that objective clinical responses can be achieved with a tolerable level of side effects, even at high viral doses. The more clinically adaptable intravenous route of administration also appears to be as well tolerated as the more challenging intratumoural injections. Conclusion Published clinical trials provide data of the safety and some signs of oncolytic activity of conditionally-replicative adenoviruses in patients with pancreatic cancer. Importantly, on the latest trials, the easier intravenous route of administration seems to be well tolerated and safe, providing the opportunity for further clinical evaluation. It is hoped that the ongoing clinical trials will yield more promising results of this therapeutic approach against a currently intractable disease.

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A dopamine antagonist, domperidone enhances the replication of an oncolytic adenovirus in human tumour cells

Cited by 2 publications

References 23 publications

Effects of pre-existing anti-adenovirus antibodies on transgene expression levels and therapeutic efficacies of arming oncolytic adenovirus

Effects of pre-existing anti-adenovirus antibodies on transgene expression levels and therapeutic efficacies of arming oncolytic adenovirus

Oncolytic adenoviruses and the treatment of pancreatic cancer: a review of clinical trials

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