54 research outputs found
Oncolytic virotherapy - analysis, design, models
Full text linkThe deliberate use of viruses as oncolytic (cancer killing) agents has become evident since initial observations tracing back to the early 20th century. However, clinical use of therapeutic viruses requires them to be safe and effective. In this thesis, we analyzed, designed and modeled strategies to improve oncolytic virotherapy with a focus on genetically engineering Semliki Forest virus.First, we evaluated clinical evidence on the use of virotherapy, revealing the potential of genetically modified viruses to enhance safety and tumor immunogenicity, while highlighting the need for controlled studies to validate efficacy. Subsequently, we designed Semliki Forest virus-based replicon particles, capable of a single round of infection and encode immunogenic cytokines. Using various tumor-immune co-culture assays we demonstrate that these oncolytic viruses strongly boost the recruitment and activation of immune cells. Notably, we observed that infection by oncolytic viruses counteracts the immuno-suppressive nature of tumor extracellular vesicles, as a relatively unexplored mechanism of virotherapy mediated immune-activation.Next, we analyzed literature to understand various cellular and systemic mechanisms used by tumor, stromal and immune cells that undermine oncolytic virotherapy. To explore the spatiotemporal dynamics of virotherapy in presence of infection-resistant tumor cells and the resulting immune responses, we employed a computational modeling approach. Here, we show that even in few numbers, infection-resistant tumor and stromal cells impede tumor eradication by oncolytic viruses. Moreover, we demonstrate that highly effective inflammatory molecules released by infected cells, spreading rapidly are required for optimal anticancer T cell cytotoxicity throughout the tumor, resulting in tumor eradication
Therapeutic Vaccines and Cancer Immunotherapy
Full text linkCancer immunotherapy and immunization are the next steps towards safe and effective cancer treatment [...].</p
Study and Design of Integrated Mixer and LNA Topologies for WiFi and Wideband Systems with a High Immunity to Parasitic Signal Feedthrough
No full textIn the recent
years, progress in wireless technology has required high-quality receiver
designs that comprise low power, low cost, and high integration. Low noise
amplifiers (LNA) and mixers are essential components of the design of the
receiver. During this project, three integrated circuits solutions are
developed which includes four mixer circuits and two LNA topologies. The
folded mixer that is developed for WiFi applications provides high isolations
and improved linearity. The self-biased mixer, bulk-injection mixer,
switched-transconductance mixer, and LNA support the use of this design in
low-power and wideband front-end applications
Molecular Circuits of Immune Sensing and Response to Oncolytic Virotherapy
Full text linkOncolytic virotherapy is a promising immunotherapy approach for cancer treatment that utilizes viruses to preferentially infect and eliminate cancer cells while stimulating the immune response. In this review, we synthesize the current literature on the molecular circuits of immune sensing and response to oncolytic virotherapy, focusing on viral DNA or RNA sensing by infected cells, cytokine and danger-associated-signal sensing by neighboring cells, and the subsequent downstream activation of immune pathways. These sequential sense-and-response mechanisms involve the triggering of molecular sensors by viruses or infected cells to activate transcription factors and related genes for a breadth of immune responses. We describe how the molecular signals induced in the tumor upon virotherapy can trigger diverse immune signaling pathways, activating both antigen-presenting-cell-based innate and T cell-based adaptive immune responses. Insights into these complex mechanisms provide valuable knowledge for enhancing oncolytic virotherapy strategies
Studies on Surfactant–Ionic Liquid Interaction on Clouding Behaviour and Evaluation of Thermodynamic Parameters
No full textMolecular Circuits of Immune Sensing and Response to Oncolytic Virotherapy
No full textOncolytic virotherapy is a promising immunotherapy approach for cancer treatment, utilizing viruses to preferentially infect and eliminate cancer cells while stimulating immune responses. In this review we synthesize current literature on the molecular circuits of immune sensing and response to oncolytic virotherapy; focusing on viral DNA or RNA sensing by infected cells, cytokine and danger-associated signal sensing by neighboring cells, and subsequent downstream activation of immune pathways. The sequential sense-and-response mechanisms involve the triggering of molecular sensors by viruses or infected cells to activate transcription factors and related genes for a breadth of immune responses. We describe how molecular signals induced in the tumor upon virotherapy can trigger diverse immune signaling pathways, activating both antigen-presenting cell-based innate and T cell-based adaptive immune responses. Insights into these complex mechanisms provide valuable knowledge for enhancing oncolytic virotherapy strategies
Resistance Mechanisms Influencing Oncolytic Virotherapy, a Systematic Analysis:a Systematic Analysis
Full text linkResistance 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
- …
