| 1. |
- Forsberg, Elin, et al.
(författare)
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HER2 CAR-T Cells Eradicate Uveal Melanoma and T-cell Therapy-Resistant Human Melanoma in IL2 Transgenic NOD/SCID IL2 Receptor Knockout Mice
- 2019
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Ingår i: Cancer Research. - 0008-5472. ; 79:5, s. 899-904
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Tidskriftsartikel (refereegranskat)abstract
- Chimeric antigen receptors (CAR) can transmit signals akin to those from activated T-cell receptors when bound to a cell surface target. CAR-expressing T cells against CD19 can cause curative effects in leukemia and lymphoma and is approved for clinical use. However, no CAR-T therapy is currently approved for use in solid tumors. We hypothesize that the resistance of solid tumors to CAR-T can be overcome by similar means as those used to reactivate tumor-infiltrating T lymphocytes (TIL), for example, by cytokines or immune checkpoint blockade. Here we demonstrate that CAR-T cells directed against HER2 can kill uveal and cutaneous melanoma cells in vitro and in vivo. Curative effects in vivo were only observed in xenografts grown in a NOD/SCID IL2 receptor gamma (NOG) knockout mouse strain transgenic for human IL2. The effect was target-specific, as CRISPR/Cas9-mediated disruption of HER2 in the melanoma cells abrogated the killing effect of the CAR-T cells. The CAR-T cells were also able to kill melanoma cells from patients resistant to adoptive T-cell transfer (ACT) of autologous TILs. Thus, CAR-T therapy represents an option for patients that do not respond to immunotherapy with ACT of TIL or immune checkpoint blockade. In addition, our data highlight the use of IL2 transgenic NOG mice as models to prove efficacy of CAR-T-cell products, possibly even in a personalized manner. Significance: These findings demonstrate that a novel humanized mouse model can help clinical translation of CAR-T cells against uveal and cutaneous melanoma that do not respond to TIL therapy or immune checkpoint blockade.
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| 2. |
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| 3. |
- Jespersen, Henrik, et al.
(författare)
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Concomitant use of pembrolizumab and entinostat in adult patients with metastatic uveal melanoma (PEMDAC study): protocol for a multicenter phase II open label study.
- 2019
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Ingår i: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- While recent years have seen a revolution in the treatment of metastatic cutaneous melanoma, no treatment has yet been able to demonstrate any prolonged survival in metastatic uveal melanoma. Thus, metastatic uveal melanoma remains a disease with an urgent unmet medical need. Reports of treatment with immune checkpoint inhibitors have thus far been disappointing. Based on animal experiments, it is reasonable to hypothesize that the effect of immunotherapy may be augmented by epigenetic therapy. Proposed mechanisms include enhanced expression of HLA class I and cancer antigens on cancer cells, as well as suppression of myeloid suppressor cells.The PEMDAC study is a multicenter, open label phase II study assessing the efficacy of concomitant use of the PD1 inhibitor pembrolizumab and the class I HDAC inhibitor entinostat in adult patients with metastatic uveal melanoma. Primary endpoint is objective response rate. Eligible patients have histologically confirmed metastatic uveal melanoma, ECOG performance status 0-1, measurable disease as per RECIST 1.1 and may have received any number of prior therapies, with the exception of anticancer immunotherapy. Twenty nine patients will be enrolled. Patients receive pembrolizumab 200mg intravenously every third week in combination with entinostat 5mg orally once weekly. Treatment will continue until progression of disease or intolerable toxicity or for a maximum of 24months.The PEMDAC study is the first trial to assess whether the addition of an HDAC inhibitor to anti-PD1 therapy can yield objective anti-tumoral responses in metastatic UM.ClinicalTrials.gov registration number: NCT02697630 . (Registered 3 March 2016). EudraCT registration number: 2016-002114-50.
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| 4. |
- Levin, Sune, 1991, et al.
(författare)
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A nanofluidic device for parallel single nanoparticle catalysis in solution
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Studying single catalyst nanoparticles, during reaction, eliminates averaging effects that are an inherent limitation of ensemble experiments. It enables establishing structure-function correlations beyond averaged properties by including particle-specific descriptors such as defects, chemical heterogeneity and microstructure. Driven by these prospects, several single particle catalysis concepts have been implemented. However, they all have limitations such as low throughput, or that they require very low reactant concentrations and/or reaction rates. In response, we present a nanofluidic device for highly parallelized single nanoparticle catalysis in solution, based on fluorescence microscopy. Our device enables parallel scrutiny of tens of single nanoparticles, each isolated inside its own nanofluidic channel, and at tunable reaction conditions, ranging from the fully mass transport limited regime to the surface reaction limited regime. In a wider perspective, our concept provides a versatile platform for highly parallelized single particle catalysis in solution and constitutes a promising application area for nanofluidics.
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| 5. |
- Nilsson, Jan-Henrik, et al.
(författare)
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Dining in the Skies. A historical account of hospitality in aviation
- 2019
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Ingår i: Fika, Hygge and Hospitality : The cultural complexity of service organisation in the Öresund Region - The cultural complexity of service organisation in the Öresund Region. - 2001-9874. - 9789170613029 ; 39, s. 107-129
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Bokkapitel (refereegranskat)
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| 6. |
- Nilsson, Per A., 1957-
(författare)
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Studying abroad : exploring mobility, expectations and experiences among mobile students
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis deals with the experiences and outcomes of temporarily studying abroad, via follow-up studies, aiming to explore international student mobility with a focus on the individual’s perspective. The specific research questions, dealing with the individual students’ expectations and experiences, are addressed in three papers. The fourth paper is a framing of these studies, using results from a global study.The first research question connects to the attractiveness of international study experiences: Q1. What are the individual’s expectations for studying abroad, among inbound and outbound students, and what are the students’ reported experiences compared with these expectations? The second research question connects to the mobility culture of youth: Q2. Does students’ reported life satisfaction change in any way after studying abroad?A main finding for outbound students was an appreciation of courses offered at the destination higher education institution that were not available at Umeå University. The students also had a desire to change their environment and have new experiences. Conversely, the desire to work abroad in the future was lower after returning home. A major finding for inbound students was that they assigned higher value to personal development than academic development. The experience made the students positive in regard to working abroad. Inbound students reported significantly higher satisfaction at follow-up six months later for the domains somatic health and activities of daily living. For both in- and outbound students, experiencing a new culture was more important than pure academic experiences.When the experience was compared with the expectation, in most cases the outcomes were positively related for both in- and outbound students. The motives for international study were primarily related to personal achievements, indicating a fulfilment of one’s potential and curiosity about a sojourn abroad.Finally, the results from the Umeå studies were compared with a global survey. The Umeå studies shows that the respondents viewed studying abroad as an important experience and as a merit later in life. The global survey results indicate that the transition from education to the world of work is of increasing importance to students, and that it matters more for non-European students. The global study showed that employability, teaching ability, expert lectures, and course organization are important to international students.
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| 7. |
- Nilsson, R. Henrik, 1976, et al.
(författare)
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The UNITE database for molecular identification of fungi: handling dark taxa and parallel taxonomic classifications.
- 2019
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Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 47:D1
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Tidskriftsartikel (refereegranskat)abstract
- UNITE (https://unite.ut.ee/) is a web-based database and sequence management environment for the molecular identification of fungi. It targets the formal fungal barcode-the nuclear ribosomal internal transcribed spacer(ITS) region-and offers all ∼1 000000 public fungal ITS sequences for reference. These are clustered into ∼459000 species hypotheses and assigned digital object identifiers (DOIs) to promote unambiguous reference across studies. In-house and web-based third-party sequence curation and annotation have resulted in more than 275000 improvements to the data over the past 15 years. UNITE serves as a data provider for a range of metabarcoding software pipelines and regularly exchanges data with all major fungal sequence databases and other community resources. Recent improvements include redesigned handling of unclassifiable species hypotheses, integration with the taxonomic backbone of the Global Biodiversity Information Facility, and support for an unlimited number of parallel taxonomic classification systems.
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| 8. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 9. |
- Adman, Per, et al.
(författare)
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171 forskare: ”Vi vuxna bör också klimatprotestera”
- 2019
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Ingår i: Dagens nyheter (DN debatt). - Stockholm. - 1101-2447.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 26/9. Vuxna bör följa uppmaningen från ungdomarna i Fridays for future-rörelsen och protestera eftersom det politiska ledarskapet är otillräckligt. Omfattande och långvariga påtryckningar från hela samhället behövs för att få de politiskt ansvariga att utöva det ledarskap som klimatkrisen kräver, skriver 171 forskare i samhällsvetenskap och humaniora.
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| 10. |
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