The NSA’s mass surveillance program: illegal and opaque

On May 7th a panel of judges of the U.S. Court of Appeals for the Second Circuit ruled that the National Security Agency’s bulk collection of telephone metadata violated the law. Toni Locy writes that the decision is significant in that it would not have occurred but for Edward Snowden’s revelations over this mass surveillance, and that it refutes the government’s arguments that the mass collection of phone records is instrumental to its anti-terrorism efforts

Two dimensional design on thrown forms

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The re-emergenge of a Tory-court party : peers of the Bloomsbury Gang and founders of modern British conservatism

From October 1768 to April 1784, the Bloomsbury Gang, a political faction of intermarried, aristocratic families dedicated to conservative principles and patriotic sentiments, led the re-emergence of a Tory-Court party that developed into the modern Conservative party in Great Britain. These leaders founded a party of Conservative Whigs that was not ruled by, but worked in cooperation with, the monarch and his allies for almost three decades. In so doing, political opportunists such as the Duke of Bedford and the Lords Gower, Sandwich, and Weymouth, restored the English two-party system through which they maintained their dominance of eighteenth-century British society and governance

Dendritic Cells: The Tools for Cancer Treatment

During cancer immune editing, the immune system shapes tumor fate in three phases through the activation of innate and adaptive immune mechanisms. After the elimination and equilibrium phase, the escape phase represents the final phase in which immunologically sculpted tumors begin to grow progressively. In this chapter, we will discuss which efforts are made to restore the balance in favor of the immune system making use of dendritic cells (DCs). The first approach is adoptive cell transfer, in which autologous DCs are generated and activated ex vivo. Secondly, we will discuss attempts in which pro-inflammatory or pro-migratory factors are delivered to attract and activate DCs in situ. Both strategies have the general goal to activate and mature DCs able to induce a robust tumor-specific T cell response. In addition, this chapter will discuss the clinical impact of DC-based therapies in cancer treatment focusing on the safety, feasibility, immunological responses, and clinical outcome

Development of a Human Cytomegalovirus (HCMV)-Based Therapeutic Cancer Vaccine Uncovers a Previously Unsuspected Viral Block of MHC Class I Antigen Presentation

Human cytomegalovirus (HCMV) induces a uniquely high frequency of virus-specific effector/memory CD8+ T-cells, a phenomenon termed “memory inflation”. Thus, HCMV-based vaccines are particularly interesting in order to stimulate a sustained and strong cellular immune response against cancer. Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with high lethality and inevitable relapse. The current standard treatment does not significantly improve the desperate situation underlining the urgent need to develop novel approaches. Although HCMV is highly fastidious with regard to species and cell type, GBM cell lines are susceptible to HCMV. In order to generate HCMV-based therapeutic vaccine candidates, we deleted all HCMV-encoded proteins (immunoevasins) that interfere with MHC class I presentation. The aim being to use the viral vector as an adjuvant for presentation of endogenous tumor antigens, the presentation of high levels of vector-encoded neoantigens and finally the repurposing of bystander HCMV-specific CD8+ T cells to fight the tumor. As neoantigen, we exemplarily used the E6 and E7 proteins of human papillomavirus type 16 (HPV-16) as a non-transforming fusion protein (E6/E7) that covers all relevant antigenic peptides. Surprisingly, GBM cells infected with E6/E7-expressing HCMV-vectors failed to stimulate E6-specific T cells despite high level expression of E6/E7 protein. Further experiments revealed that MHC class I presentation of E6/E7 is impaired by the HCMV-vector although it lacks all known immunoevasins. We also generated HCMV-based vectors that express E6-derived peptide fused to HCMV proteins. GBM cells infected with these vectors efficiently stimulated E6-specific T cells. Thus, fusion of antigenic sequences to HCMV proteins is required for efficient presentation via MHC class I molecules during infection. Taken together, these results provide the preclinical basis for development of HCMV-based vaccines and also reveal a novel HCMV-encoded block of MHC class I presentation