Browsing by Subject "antitumor effect"

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  • Vainionpää, Teea (Helsingfors universitet, 2016)
    Oncolytic viruses have been extensively studied for the treatment of cancer. They are genetically engineered viruses, which are able to selectively infect and kill the cancer cells causing no harm to normal cells. Adenoviruses are the most commonly used viruses in the gene therapy field and their oncolytic variants are currently under evaluation in many clinical trials. The cell killing properties of oncolytic adenoviruses against the cancer cells have been known for a long time. In addition, it is known that they can activate immune system. To achieve more selective and effective antitumor effects several modifications of oncolytic adenoviruses have been studied. During my internship I worked on the development of a new cancer vaccine platform based on peptide-coated conditionally replicating adenovirus (PeptiCRAd). The PeptiCRAd technology consists of a serotype 5 adenoviruses which are coated with tumorderived peptides. The aim of the thesis was to evaluate the antitumor efficacy of the PeptiCRAd. The cytopathic effects of the PeptiCRAd were studied in vitro using human adenocarcinoma cell line, A549. In this experiment three different treatments were used to study the cytopathic effects of the PeptiCRAd and Ad5Δ24-CpG- virus or polyK-SIINFEKL- peptide alone. The cell viability was assayed using MTS reagent and quantified by spectrophotometer. The antitumor effects were also studied in vivo using immunocompetent C57BL/6 mice bearing B16-OVA melanoma tumors. Tumor-bearing mice were treated with Ad5Δ24-CpG- virus, SIINFEKL- peptide or the PeptiCRAd. To evaluate the antitumor effects, tumor volume was observed after the treatments. In this study, I show that PeptiCRAd and Ad5Δ24-CpG- virus both have oncolytic effects in vitro against A549 cells. In vitro Ad5Δ24-CpG- virus showed significantly better cytopathic effects at high concentration compared to PeptiCRAd. In vivo the PeptiCRAd showed strongest antitumor effect on the growth of established tumors. At the end of the experiment the volume of the tumor was significantly smallest in the PeptiCRAd group.