A phase I/II study of Enadenotucirev, an oncolytic Ad11/Ad3 chimeric group B adenovirus, administered intraperitoneally (IP): Dose finding and proof of concept in platinum-resistant epithelial ovarian cancer.

McNeish, Iain A.; Michael, Agnieszka; Twelves, Chris; Glasspool, Rosalind; Ajaz, Mazhar; Morrison, Rebecca; Xeniou, Ourania; Brown, R. H.; Fisher, Kerry; Blanc, C.

doi:10.1200/jco.2015.33.15_suppl.tps5611

Cited by 2 publications

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“…Enadenotucirev is active against a wide range of epithelial-derived tumours, and has been investigated clinically in multiple indications including colorectal, ovarian, lung, bladder and renal carcinoma [ 32 , 38 , 39 ]. While enadenotucirev is broadly active in carcinomas it is also highly selective for human tumour cells of epithelial origin over healthy human non-tumour cells (primary or cell lines) or mouse tumour cells.…”

Section: Resultsmentioning

confidence: 99%

Development of a versatile oncolytic virus platform for local intra-tumoural expression of therapeutic transgenes

et al. 2017

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Oncolytic viruses which infect and kill tumour cells can also be genetically modified to express therapeutic genes that augment their anti-cancer activities. Modifying oncolytic viruses to produce effective cancer therapies is challenging as encoding transgenes often attenuates virus activity or prevents systemic delivery in patients due to the risk of off-target expression of transgenes in healthy tissues. To overcome these issues we aimed to generate a readily modifiable virus platform using the oncolytic adenovirus, enadenotucirev. Enadenotucirev replicates in human tumour cells but not cells from healthy tissues and can be delivered intravenously because it is stable in human blood. Here, the enadenotucirev genome was used to generate plasmids into which synthesised transgene cassettes could be directly cloned in a single step reaction. The platform enabled generation of panels of reporter viruses to identify cloning sites and transgene cassette designs where transgene expression could be linked to the virus life cycle. It was demonstrated using these viruses that encoded transgene proteins could be successfully expressed in tumour cells in vitro and tumours in vivo. The expression of transgenes did not impact either the oncolytic activity or selective properties of the virus. The effectiveness of this approach as a drug delivery platform for complex therapeutics was demonstrated by inserting multiple genes in the virus genome to encode full length anti-VEGF antibodies. Functional antibody could be synthesised and secreted from infected tumour cells without impacting the activity of the virus particle in terms of oncolytic potency, manufacturing yields or selectivity for tumour cells. In vivo, viral particles could be efficaciously delivered intravenously to disseminated orthotopic tumours.

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Section: Resultsmentioning

confidence: 99%

Development of a versatile oncolytic virus platform for local intra-tumoural expression of therapeutic transgenes

et al. 2017

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Integrating Cancer Vaccines in the Standard-of-Care of Ovarian Cancer: Translating Preclinical Models to Human

Chiang

Rovelli

Sarivalasis

et al. 2021

Cancers

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As the majority of ovarian cancer (OC) patients are diagnosed with metastatic disease, less than 40% will survive past 5 years after diagnosis. OC is characterized by a succession of remissions and recurrences. The most promising time point for immunotherapeutic interventions in OC is following debulking surgery. Accumulating evidence shows that T cells are important in OC; thus, cancer vaccines capable of eliciting antitumor T cells will be effective in OC treatment. In this review, we discuss different cancer vaccines and propose strategies for their incorporation into the OC standard-of-care regimens. Using the murine ID8 ovarian tumor model, we provide evidence that a cancer vaccine can be effectively combined with OC standard-of-care to achieve greater overall efficacy. We demonstrate several important similarities between the ID8 model and OC patients, in terms of response to immunotherapies, and the ID8 model can be an important tool for evaluating combinatorial regimens and clinical trial designs in OC. Other emerging models, including patient-derived xenograft and genetically engineered mouse models, are continuing to improve and can be useful for evaluating cancer vaccination therapies in the near future. Here, we provide a comprehensive review of the completed and current clinical trials evaluating cancer vaccines in OC.

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A phase I/II study of Enadenotucirev, an oncolytic Ad11/Ad3 chimeric group B adenovirus, administered intraperitoneally (IP): Dose finding and proof of concept in platinum-resistant epithelial ovarian cancer.

Cited by 2 publications

References 0 publications

Development of a versatile oncolytic virus platform for local intra-tumoural expression of therapeutic transgenes

Development of a versatile oncolytic virus platform for local intra-tumoural expression of therapeutic transgenes

Integrating Cancer Vaccines in the Standard-of-Care of Ovarian Cancer: Translating Preclinical Models to Human

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