DNA vaccination for prostate cancer: key concepts and considerations

While locally confined prostate cancer is associated with a low five year mortality rate, advanced or metastatic disease remains a major challenge for healthcare professionals to treat and is usually terminal. As such, there is a need for the development of new, efficacious therapies for prostate cancer. Immunotherapy represents a promising approach where the host’s immune system is harnessed to mount an anti-tumour effect, and the licensing of the first prostate cancer specific immunotherapy in 2010 has opened the door for other immunotherapies to gain regulatory approval. Among these strategies DNA vaccines are an attractive option in terms of their ability to elicit a highly specific, potent and wide-sweeping immune response. Several DNA vaccines have been tested for prostate cancer and while they have demonstrated a good safety profile they have faced problems with low efficacy and immunogenicity compared to other immunotherapeutic approaches. This review focuses on the positive aspects of DNA vaccines for prostate cancer that have been assessed in preclinical and clinical trials thus far and examines the key considerations that must be employed to improve the efficacy and immunogenicity of these vaccines

Vaccine delivery by penetratin: mechanism of antigen presentation by dendritic cells

Cell-penetrating peptides (CPP) or membrane-translocating peptides such as penetratin from Antennapedia homeodomain or TAT from human immunodeficiency virus are useful vectors for the delivery of protein antigens or their cytotoxic (Tc) or helper (Th) T cell epitopes to antigen-presenting cells. Mice immunized with CPP containing immunogens elicit antigen-specific Tc and/or Th responses and could be protected from tumor challenges. In the present paper, we investigate the mechanism of class I and class II antigen presentation of ovalbumin covalently linked to penetratin (AntpOVA) by bone marrow-derived dendritic cells with the use of biochemical inhibitors of various pathways of antigen processing and presentation. Results from our study suggested that uptake of AntpOVA is via a combination of energy-independent (membrane fusion) and energy-dependent pathways (endocytosis). Once internalized by either mechanism, multiple tap-dependent or independent antigen presentation pathways are accessed while not completely dependent on proteasomal processing but involving proteolytic trimming in the ER and Golgi compartments. Our study provides an understanding on the mechanism of antigen presentation mediated by CPP and leads to greater insights into future development of vaccine formulations

Abundances of large microplastics (L-MP, 500-5000 µm) in surface waters of the Weser estuary and the German North Sea (April 2018)

In order to assess pollution with large microplastics (L-MP, 500-5000 µm) in the Lower Weser and transition to the German North Sea, surface water samples were collected with the RV Otzum (ICBM, Institute for Chemistry and Biology of the Marine Environment), as well as with the RV Uthörn (AWI, Alfred-Wegener-Institute) in April 2018. Sampling was performed using a microplastic net (mesh size: 300 µm), followed by filtration in the laboratory over a 500 µm stainless steel sieve. Putative MP items in the size range 500-5000 µm were analysed by means of Attenuated Total Reflection - FTIR in order to determine the underlying synthetic polymer. Dominant polymer type in the L-MP sample fraction was polyethylene. Concentrations ranged between 1 × 10-2 m-3 and 9.8 × 10-1 m-3. The highest MP concentration was measured upstream the Weser Weir

Abundances of small microplastics (S-MP, 11-500 µm) in surface waters of the Weser estuary and the German North Sea (April 2018)

In order to assess pollution with small microplastics (S-MP, 11-500 µm) in the Lower Weser and transition to the German North Sea, surface water samples were collected with the RV Otzum (ICBM, Institute for Chemistry and Biology of the Marine Environment), as well as with the RV Uthörn (AWI, Alfred-Wegener-Institute) in April 2018. Sampling was performed using a pumping system containing of a floating suction basket (mesh size: 500 µm) for pre-filtration, followed by the concentration onto a 15 µm stainless steel screen. Samples were isolated from the filter screens in the laboratory, thoroughly processed and measured via µFTIR imaging. Dominant polymer type in the S-MP sample fraction was acrylates/polyurethanes/varnish, and concentrations ranged between 2.3 × 10¹ and 9.7 × 10³ m⁻³, with maximum values in the area of the turbidity Maximum Zone of the River Weser