Resistance Mechanisms Influencing Oncolytic Virotherapy, a Systematic Analysis:a Systematic Analysis

Resistance to therapy is a frequently observed phenomenon in the treatment of cancer, and as with other cancer therapeutics, therapies based on oncolytic viruses also face the challenges of resistance, such as humoral and cellular antiviral responses, and tumor-associated interferon-mediated resistance. In order to identify additional mechanisms of resistance that may contribute to therapeutic failure, we developed a systematic search strategy for studies published in PubMed. We analyzed 6143 articles on oncolytic virotherapy and found that approximately 8% of these articles use resistance terms in the abstract and/or title. Of these 439 articles, 87 were original research. Most of the findings reported pertain to resistance mediated by tumor-cell-dependent interferon signaling. Yet, mechanisms such as epigenetic modifications, hypoxia-mediated inhibition, APOBEC-mediated resistance, virus entry barriers, and spatiotemporal restriction to viral spread, although not frequently assessed, were demonstrated to play a major role in resistance. Similarly, our results suggest that the stromal compartment consisting of, but not limited to, myeloid cells, fibroblasts, and epithelial cells requires more study in relation to therapy resistance using oncolytic viruses. Thus, our findings emphasize the need to assess the stromal compartment and to identify novel mechanisms that play an important role in conferring resistance to oncolytic virotherapy

A systematic analysis on the clinical safety and efficacy of onco-virotherapy

Several onco-virotherapy candidates have been developed and clinically evaluated for the treatment of cancer, and several are approved for clinical use. In this systematic review we explored the clinical impact of onco-virotherapy compared to other cancer therapies by analyzing factors such as trial design, patient background, therapy design, delivery strategies, and study outcomes. For this purpose, we retrieved clinical studies from three platforms: ClinicalTrials.gov, PubMed, and EMBASE. We found that most studies were performed in patients with advanced and metastatic tumors, using a broad range of genetically engineered vectors and mainly administered intratumorally. Therapeutic safety was the most frequently assessed outcome, while relatively few studies focused on immunological antitumor responses. Moreover, only 59 out of 896 clinical studies were randomized controlled trials reporting comparative data. This systemic review thus reveals the need of more, and better controlled, clinical studies to increase our understanding on the application of onco-virotherapy either as a single treatment or in combination with other cancer immunotherapies

Ionic liquid mediated cloud point extraction of Blue BG dye

1409-1413<span style="font-size:9.0pt;font-family: " times="" new="" roman","serif";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-us;mso-fareast-language:en-us;mso-bidi-language:hi"="" lang="EN-US">Cloud point extraction has been adopted for the separation of Blue BG dye using the ionic liquid, tetraethyl ammonium tetrafluoroborate, as an additive with non-ionic surfactant Triton X-100. The effects of various operating parameters such as temperature, time and concentrations of surfactant, dye and IL on extraction of dye have been studied in detail to find out the optimum conditions. The extraction of dye is found to increase with increase in temperature, time, surfactant concentration and IL concentration. The Langmuir isotherm has been used to compute the feed surfactant concentration required for the removal of Blue BG dye up to an extraction efficiency of 90%. The effects of temperature and concentration of surfactant on various thermodynamic parameters have been examined; the values of G0  increases with temperature and decreases with surfactant concentration. The values of H0  and S0  increase with surfactant concentration.</span

Oncolytic alphavirus replicons mediated recruitment and activation of T cells

Summary: Oncolytic viruses show promise in enhancing tumor immunogenicity by releasing immunogenic signals during tumor cell infection and lysis. In this study, we improved the virus-induced tumor immunogenicity of recombinant Semliki Forest virus (rSFV)-based replicon particles by encoding immunogenic cytokines such as C-X-C motif chemokine ligand 10 (CXCL10), FMS-like tyrosine kinase 3 ligand (Flt3L), or interferon-gamma (IFN-ƴ). Real-time imaging and flow cytometry of human cancer cell-based monolayer and spheroid cultures, using LNCaP or PANC-1 cells, revealed effective infection and transgene expression in both models. LNCaP cells exhibited higher and earlier rSFV infection compared to PANC-1 cells. While infected LNCaP cells effectively triggered immune recruitment and T cell activation even without encoding cytokines, PANC-1 cells demonstrated improved immune responses only when infected with replicons encoding cytokines, particularly IFN-ƴ, which enhanced tumor immunogenicity irrespective of cancer cell susceptibility to infection. Our study demonstrates that despite innate phenotypic disparities in cancer cells, rSFV-based replicons encoding cytokines can potentially generate effective immune responses in the tumor

Extraction of essential oil from Patchouli leaves using hydrodistillation: Parametric studies and optimization

Hydrodistillation has been employed for the extraction of essential oil from the leaves of patchouli plant. The yield of patchouli oil is dependent on solid loading, water volume, size of leaves and extraction time. The optimization of the process parameters has been performed using the Taguchi method while analysis of variance is used to identify the impact of parameters on the yield. The highest yield of patchouli oil (1.53%, w/w) is found at 30 g of solid loading, 900 mL of water volume, 4 mm size of the leaves and 150 min of extraction time. Among the parameters studied, extraction time had a greater impact on the yield of patchouli oil. Amount of patchoulol is maximum (64.9%) in the essential oil obtained under optimized conditions, thus, providing better quality of the essential oil

Extraction of essential oil from Patchouli leaves using hydrodistillation: Parametric studies and optimization

405-410Hydrodistillation has been employed for the extraction of essential oil from the leaves of patchouli plant. The yield of patchouli oil is dependent on solid loading, water volume, size of leaves and extraction time. The optimization of the process parameters has been performed using the Taguchi method while analysis of variance is used to identify the impact of parameters on the yield. The highest yield of patchouli oil (1.53%, w/w) is found at 30 g of solid loading, 900 mL of water volume, 4 mm size of the leaves and 150 min of extraction time. Among the parameters studied, extraction time had a greater impact on the yield of patchouli oil. Amount of patchoulol is maximum (64.9%) in the essential oil obtained under optimized conditions, thus, providing better quality of the essential oil