Aero-Thermo-Structural Trade-Off Studies for Hypersonic Transport Gliders based on the DLR SpaceLiner Concept

The Space Launcher Systems Analysis Group SART of the German Aerospace Center DLR has been working for several years on developing a novel hypersonic passenger transportation concept. The SpaceLiner, originally proposed in 2005, is a two staged, rocket propelled and vertical take-off transportation system designed for a 90 minutes Europe-Australia reference mission carrying 50 passengers. The SpaceLiner has gone through several design cycles, with the most recent configuration SpaceLiner7-3 currently under definition. Various papers on the vehicle design as well as design of individual subsystems have been published over the years. One important finding was the high level of interdependency of the different technical disciplines and subsystems within a large design space, which on the one hand complicates the identification of optimum design solutions, while on the other hand offering unexpected performance increase potentials. Therefore, the work presented in this paper will leave the baseline configuration of the SpaceLiner and perform parametric system studies on a broader level. The aim is to identify and quantify interactions and interdependencies within the design space in order to provide design improvements for a potential future SpaceLiner configuration, as well as for vehicles of this class in general. Thereby, this work will investigate the design task on a pure parametric way due to the high complexity of the problem. An automated system analysis loop is utilized, but no multi-disciplinary optimization procedures will be applied. The parametric studies are still in progress, with first results being presented in this paper

Lentiviral vectors for induction of self-differentiation and conditional ablation of dendritic cells

Development of lentiviral vectors (LVs) in the field of immunotherapy and immune regeneration will strongly rely on biosafety of the gene transfer. We demonstrated previously the feasibility of ex vivo genetic programming of mouse bone marrow precursors with LVs encoding granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4), which induced autonomous differentiation of long-lived dendritic cells (DCs), referred to as self-differentiated myeloid-derived antigen-presenting-cells reactive against tumors (SMART-DCs). Here, LV biosafety was enhanced by using a DC-restricted and physiological promoter, the major histocompatibility complex (MHC) II promoter, and including co-expression of the herpes simplex virus-thymidine kinase (sr39HSV-TK) conditional suicide gene. Tricistronic vectors co-expressing sr39HSV-TK, GM-CSF and IL-4 transcriptionally regulated by the MHCII promoter or the ubiquitous cytomegalovirus (CMV) promoter were compared. Despite the different gene transfer effects, such as the kinetics, levels of transgene expression and persistency of integrated vector copies, both vectors induced highly viable SMART-DCs, which persisted for at least 70 days in vivo and could be ablated with the pro-drug Ganciclovir (GCV). SMART-DCs co-expressing the tyrosine-related protein 2 melanoma antigen administered subcutaneously generated antigen-specific, anti-melanoma protective and therapeutic responses in the mouse B16 melanoma model. GCV administration after immunotherapy did not abrogate DC vaccination efficacy. This demonstrates proof-of-principle of genetically programmed DCs that can be ablated pharmacologically

The innovative evolution of cancer gene and cellular therapies

We provide an overview of the latest developments in cancer gene therapy--from the bench to early-stage clinical trials. We describe the most recent work of worldwide teams including experienced scientists and clinicians, reflecting the recent emergence of gene therapy from the 'Valley of Death'. The treatment efficacy of clinical gene therapy has now been shown in a number of diseases including cancer and we are observing a renewed interest by big pharmaceutical and biotechnology companies most obviously demonstrated by Amgen's acquisition of Biovex for up to USD$1 billion. There is an opportunity to be cautiously hopeful regarding the future of gene therapy in the clinic and we review here some of the most recent progress in the field