A Commentary on Hegelian Philosophy and the Absolutes in Law

The principles of law are twofold: those that are absolute and those that are relative. The absolute and the relative are akin to dogma and doctrine, respectively. We are on shaky ground indeed when we stand upon relativism. The principal purveyors of relativism have been Justices Cardozo, Douglas, and Holmes

The Hohfeldian Approach to Constitutional Cases

INFERRED, OR AT THE MOST rebuttably presumed, is a slight acquaintanceship on the part of the reader with the work on jural opposites and jural correlatives by Professor W. Newcomb Hohfeld. The Founding Fathers, as though anticipating the coming of the Messianic logician, used all of the four Hohfeldian gravamen terms-rights, privileges, powers and immunities-in the Constitution of the United States,\u27 and for this reason the author perceives a nexus between Hohfeldian logic and constitutional construction. The appropriate initial touchstone for contemporary use of this theory could appear to be the 1968 case of Flast v. Cohen, considering Mr. Justice Harlan\u27s allusions to Hohfeld in his dissenting opinion

The Legal and Political Foundations and Meaning of President Wilson\u27s Great Western Tour

September 4, 1919 is a red-letter date in history. On that date President Woodrow Wilson, wearing a sailor straw hat after Labor Day revealed his famous smile when he arrived in Columbus, Ohio. There, he delivered the first of forty-two speeches which concluded on September 25, in Pueblo, Colorado. Those twenty-two days marked the most memorable train trip in history - President Wilson\u27s Great Western Tour: a journey through sixteen states aboard the special seven-car Presidential train, the Mayflower. The train was aptly named, for the President\u27s speaking tour symbolized the hope of the world, just as the Pilgrims\u27 hope led them to set forth for the New World hundreds of years before

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