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

The water vapor equilibrium in the phosphoric acid \u2013 water system

For high temperature polymer electrolyte fuel cells (HT-PEFCs), phosphoric acid (PA, H3PO4) is still the state-of-the-art electrolyte material, since it shows excellent proton conductivity [1] in the temperature range between 373 K and 473 K. Another advantage is the chemical compatibility with polymers which is exceptional considering the acidity of the acid (pH < 0 unless highly diluted). However, care has to be taken that strongly dehydrating conditions have to be avoided when using PA in HT-PEFCs, since enhanced degradation of the catalyst [2] appears for these conditions. This can be explained with the formation of PA condensates [3], which are formed at low water contents and high temperatures, typically above 390 K. It is therefore crucial to avoid the formation of PA condensates by adjusting the operating conditions of a HT-PEFC. In this work, PA is exposed at a constant water vapor pressure of 10 kPa until equilibration is reached at different temperatures in the range between 333 K and 433 K. The equilibration time and the evolution of the electrical parameters during the equilibration process are discussed with respect to the water content at the end of the tests. The results not only show the formation of PA condensates for temperatures above 413 K, but also indicate the existence of a local PA hemihydrate structure occurring in the liquid before condensation occurs