| 1. |
- Foord, Emelie, et al.
(författare)
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Profound Functional Suppression of Tumor-Infiltrating T-Cells in Ovarian Cancer Patients Can Be Reversed Using PD-1-Blocking Antibodies or DARPin (R) Proteins
- 2020
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Ingår i: Journal of Immunology Research. - : Hindawi Limited. - 2314-8861 .- 2314-7156. ; 2020
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Tidskriftsartikel (refereegranskat)abstract
- PD-1/PD-L1 blockade has revolutionized the field of immunooncology. Despite the relative success, the response rate to anti-PD-1 therapy requires further improvements. Our aim was to explore the enhancement of T-cell function by using novel PD-1-blocking proteins and compare with clinically approved monoclonal antibodies (mAbs). We isolated T-cells from the ascites and tumor of 17 patients with advanced epithelial ovarian cancer (EOC) and analyzed the effects using the mAbs nivolumab and pembrolizumab and two novel engineered ankyrin repeat proteins (DARPin (R) proteins). PD-1 blockade with either mAb or DARPin (R) molecule significantly increased the release of IFN-gamma, granzyme B, IL-2, and TNF-alpha, demonstrating successful reinvigoration. The monovalent DARPin (R) protein was less effective compared to its bivalent equivalent, demonstrating that bivalency brings an additional benefit to PD-1 blockade. Overall, we found a higher fold increase of lymphokine secretion in response to the PD-1 blockade by tumor-derived T-cells; however, the absolute amounts were significantly lower compared to the release from ascites-derived T-cells. Our results demonstrate that PD-1 blockade can only partially reinvigorate functionally suppressed T-cells from EOC patients. This warrants further investigation preferably in combination with other therapeutics. The study provides an early pilot proof-of-concept for the potential use of DARPin (R) proteins as eligible alternative scaffold proteins to block PD-1.
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| 2. |
- Trydeman Knudsen, Marie, et al.
(författare)
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Characterization factors for land use impacts on biodiversity in life cycle assessment based on direct measures of plant species richness in European farmland in the ‘Temperate Broadleaf and Mixed Forest`.
- 2017
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 580, s. 358-366
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Tidskriftsartikel (refereegranskat)abstract
- Life Cycle Assessment (LCA) is a widely used tool to assess environmental sustainability of products. The LCAshould optimally cover themost important environmental impact categories such as climate change, eutrophicationand biodiversity. However, impacts on biodiversity are seldom included in LCAs due tomethodological limitationsand lack of appropriate characterization factors. When assessing organic agricultural products theomission of biodiversity in LCA is problematic, because organic systems are characterized by higher species richnessat field level compared to the conventional systems. Thus, there is a need for characterization factors to estimateland use impacts on biodiversity in life cycle assessment that are able to distinguish between organic andconventional agricultural land use that can be used to supplement and validate the few currently suggested characterization factors. Based on a unique dataset derived fromfield recording of plant species diversity in farmlandacross six European countries, the present study provides newmidpoint occupation Characterization Factors(CF) expressing the Potentially Disappeared Fraction (PDF) to estimate land use impacts on biodiversity in the‘Temperate Broadleaf and Mixed Forest’ biome in Europe. The method is based on calculation of plant specieson randomly selected test sites in the biome and enables the calculation of characterization factors that are sensitiveto particular types ofmanagement.While species richness differs between countries, the calculated CFs areable to distinguish between different land use types (pastures (monocotyledons or mixed), arable land andhedges) and management practices (organic or conventional production systems) across countries. The new occupationCFs can be used to supplement or validate the fewcurrent CF's and can be applied in LCAs of agriculturalproducts to assess land use impacts on species richness in the ‘Temperate Broadleaf and Mixed Forest’ biome.
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