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

Policies for Progress Featured Speaker Lecture

Barbara Kline Pope is the Executive Director of the Office of Communication for the National Academies and the Executive Director of the National Academies Press. She has served as NAP\u27s Marketing Director for 12 years, and has been using the Web as a dissemination, outreach, and marketing tool since its inception. Barbara is a key proponent of targeted open access to increase dissemination, and she has helped shape online publishing for more than a decade. Barbara spoke about the science of science communication and how communication-oriented research from the social and behavioral sciences informs her communication efforts at the National Academies of Sciences, Engineering, and Medicine. The policy work at the Academies was front and center as she provided examples of communication products and dissemination campaigns designed with audience relevance and impact in mind

Grand Challenges Conference Featured Speakers

A talk on Driving Impact through Scientific Communications with Barbara Kline Pope, executive director for communications at the National Academies of Sciences, Engineering, and Medicine and executive director of the National Academies Press, and Dietram Scheufele, the John E. Ross Professor in Science Communication and Vilas Distinguished Achievement Professor at the University of Wisconsin-Madison and in the Morgridge Institute for Research

—Pricing Digital Content Product Lines: A Model and Application for the National Academies Press

We examine the problem of how a content provider, specifically the National Academies Press (NAP), can optimally price the different forms of its product—print and PDF—that it sells online. Whereas products in the traditional product line generally tend to be substitutes, the different content product forms could range from being substitutes to being complements across customers. Thus the content provider can possibly sell bundles of the product forms, leading to additional revenue. We first discuss NAP's decision context and describe the model we proposed for developing NAP's optimal pricing policies for its different forms. We describe the choice experiment we conducted on the publisher's website that maximally uses the online interface to collect relevant data needed to estimate our model. We show how NAP embraced the results from the model for developing a new business model and how it used the insights derived from the study to set pricing policies and monitor sales performance as a function of pricing. Finally, we perform validation of the model and the implemented policies using dynamic modeling of sales data from NAP's website. The paper illustrates how e-commerce technologies can lead to the development of optimal policies using marketing models.pricing, product line, digital products, product form, bundling, choice experiment, Internet

Grand Challenges Conference Opening Remarks & Panel 1

Opening Remarks: Peter C. Froehlich, MBA, Director, Scholarly Publishing Purdue University Libraries Laurel Weldon, PhD., Distinguished Professor of Political Science, Purdue University, Director Purdue Policy Research Institute (PPRI) A panel discussion on Innovative Models for Research on Grand Challenges: Interdisciplinarity, Communication, Impact with Arden Bement, former director of Purdue\u27s Global Policy Research Institute, chief global affairs officer emeritus, and the David A. Ross Distinguished Professor Emeritus of Nuclear Engineering; Barbara Kline Pope, executive director for communications at the National Academies of Sciences, Engineering, and Medicine and executive director of the National Academies Press; and Nicholas Haan, track chair for Global Grand Challenges, managing director of Global Solutions Program, and on the faculty at Singularity University. The moderator was Tomás Díaz de la Rubia, chief scientist and executive director of Purdue\u27s Discovery Park