Abstract
Background: The prognosis of patients with peritoneal metastases is poor. Treatment options are limited because systemically delivered chemotherapy is not usually effective in this type of disease. Pressurised intraperitoneal aerosolised chemotherapy (PIPAC) is a recently developed alternative technology for delivering intraperitoneal chemotherapy, potentially enhancing treatment efficacy. Here, we assess the feasibility of pressurised intraperitoneal aerosolised virotherapy (PIPAV) to deliver a different class of anticancer agents, oncolytic adenoviruses, in vitro and in vivo. Methods: Adenoviral vectors expressing reporter genes green fluorescence protein (Ad5.GFP) or firefly luciferase (Ad5.Luc) were subject to pressurised aerosolisation. The ability of the virus to survive PIPAV was assessed in vitro and in vivo by monitoring reporter gene activity. Wistar rats subjected to PIPAV were assessed for any adverse procedure related events. Results: In vitro transduction assays demonstrated that Ad5 retained viability following pressurised aerosolisation and could transduce permissive cells equally effectively as non-aerosolised control vector. PIPAV was well tolerated in rats, although minimal transduction was observed following intraperitoneal administration. Conclusions: PIPAV appears viable and well tolerated, though in vivo efficacy requires further optimisation.
Highlights
Following infection of the CHO cells with aerosolised and non-aerosolised samples of adenovirus serotype 5 (Ad5).Green Fluorescent Protein (GFP), flow cytometry was carried out to compare the number of cells expressing
Gating for the flow cytometry was carried out using the control cell populations, which were not exposed to virus, but maintained in complete medium
The same pattern of GFP expression was observed in samples infected with aerosolised virus, suggesting that aerosolisation has no intrinsic effect on the virus fitness
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Malignant cells from an intra-abdominal primary tumour may invade the serosal lining of the abdominal cavity causing peritoneal metastases (PM). PM are a late feature of many cancers, making them common. They are challenging to treat, and prognosis is generally poor. The reported 5-year survival rate for patients with isolated peritoneal metastases from colorectal cancer treated with systemic chemotherapy ranges from 0 to 19% [1]. In patients with stage III ovarian cancer (i.e., spread to the abdominal cavity) the average 5 year survival rate reported is 39% [1]. Peritoneal metastases represent an area of significant unmet clinical need
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