31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Immersive Technology for Human-Centric Cyberphysical Systems in Complex Manufacturing Processes: A Comprehensive Overview of the Global Patent Profile Using Collective Intelligence

Immersive technology for human-centric cyberphysical systems includes broad concepts that enable users in the physical world to connect with the cyberworld with a sense of immersion. Complex systems such as virtual reality, augmented reality, brain-computer interfaces, and brain-machine interfaces are emerging as immersive technologies that have the potential for improving manufacturing systems. Industry 4.0 includes all technologies, standards, and frameworks for the fourth industrial revolution to facilitate intelligent manufacturing. Industrial immersive technologies will be used for smart manufacturing innovation in the context of Industry 4.0’s human machine interfaces. This research provides a thorough review of the literature, construction of a domain ontology, presentation of patent metatrend statistical analysis, and data mining analysis using a technology function matrix and highlights technical and functional development trends using latent Dirichlet allocation (LDA) models. A total of 179 references from the IEEE and IET databases and 2,672 patents are systematically analyzed to identify current trends. The paper establishes an essential foundation for the development of advanced human-centric cyberphysical systems in complex manufacturing processes

A patent quality analysis for innovative technology and product development

a b s t r a c t Enterprises evaluate intellectual property rights and the quality of patent documents in order to develop innovative products and discover state-of-the-art technology trends. The product technologies covered by patent claims are protected by law, and the quality of the patent insures against infringement by competitors while increasing the worth of the invention. Thus, patent quality analysis provides a means by which companies determine whether or not to customize and manufacture innovative products. Since patents provide significant financial protection for businesses, the number of patents filed is increasing at a fast pace. Companies which cannot process patent information or fail to protect their innovations by filing patents lose market competitiveness. Current patent research is needed to estimate the quality of patent documents. The purpose of this research is to improve the analysis and ranking of patent quality. The first step of the proposed methodology is to collect technology specific patents and to extract relevant patent quality performance indicators. The second step is to identify the key impact factors using principal component analysis. These factors are then used as the input parameters for a back-propagation neural network model. Patent transactions help judge patent quality and patents which are licensed or sold with intellectual property usage rights are considered high quality patents. This research collected 283 patents sold or licensed from the news of patent transactions and 116 patents which were unsold but belong to the technology specific domains of interest. After training the patent quality model, 36 historical patents are used to verify the performance of the trained model. The match between the analytical results and the actual trading status reached an 85% level of accuracy. Thus, the proposed patent quality methodology evaluates the quality of patents automatically and effectively as a preliminary screening solution. The approach saves domain experts valuable time targeting high value patents for R&amp;D commercialization and mass customization of products

A VR-Enabled Chatbot Supporting Design and Manufacturing of Large and Complex Power Transformers

Virtual reality (VR) immersive technology allows users to experience enhanced reality using human–computer interfaces (HCI). Many systems have implemented VR with improved HCI to provide strategic market advantages for industry and engineering applications. An intelligent chatbot is a conversational system capable of natural language communication allowing users to ask questions and receive answers online to enhance customer services. This research develops and implements a system framework for a VR-enabled large industrial power transformer mass-customization chatbot. The research collected 1272 frequently asked questions (FAQs) from a power transformer manufacturers’ knowledge base that is used for question matching and answer retrieval. More than 1.2 million Wikipedia engineering pages were used to train a word-embedding model for natural language understanding of question intent. The complex engineering questions and answers are integrated with an immersive VR computer human interface. The system enables users to ask questions and receive explicit and detailed answers combined with 3D immersive images of industrial sized power transformer assemblies. The user interfaces can be projected into the VR headwear or computer screen and manipulated with a controller. The unique immersive VR consultation chatbot system is to support real-time design consultation for the design and manufacturing of complex power transformers