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| 2. |
- Bjarnegård, Elin, 1976-, et al.
(författare)
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Gender, peace and armed conflict
- 2015
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Ingår i: SIPRI Yearbook 2015. - Oxford : Oxford University Press. - 9780198737810 ; , s. 101-109
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Bokkapitel (refereegranskat)
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| 3. |
- Forsberg, Christer, et al.
(författare)
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Principle, calibration, and application of the in situ alkali chloride monitor
- 2009
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Ingår i: Review of Scientific Instruments. - : American Institute of Physics. - 0034-6748 .- 1089-7623. ; 80:2, s. 023104-1-023104-4
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Tidskriftsartikel (refereegranskat)abstract
- The extended use of biomass for heat and power production has caused increased operational problems with fouling and high-temperature corrosion in boilers. These problems are mainly related to the presence of alkali chlorides (KCl and NaCl) at high concentrations in the flue gas. The In-Situ Alkali Chloride Monitor (IACM) was developed by Vattenfall Research and Development AB for measuring the alkali chloride concentration in hot flue gases (>650 oC). The measurement technique is based on molecular differential absorption spectroscopy in the UV range. Simultaneous measurement of SO2 concentration is also possible. The measuring range is 1-50 ppm for the sum of KCl and NaCl concentrations, and 4-750 ppm for SO2. This paper describes the principle of the IACM as well as its calibration. Furthermore, an example of its application in an industrial boiler is given.
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| 4. |
- Forsberg, Elin, 1981-
(författare)
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Blöttjan och Kimsjön
- 2008
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Ingår i: Namn från land och stad. - Uppsala : Uppsala universitet. - 9789150620122 ; , s. 63-66
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 5. |
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| 6. |
- 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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| 7. |
- Forsberg, Elin
(författare)
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Novel immunotherapies for metastatic melanoma - from mouse models towards clinical trials
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Immunotherapies including checkpoint blockade and adoptive T cell transfer (ACT) show great promise for the treatment of melanoma, with long-term effects in some patients. However, around half of the patients with metastatic malignant melanoma will not be cured with available therapies today, and these patients require other treatment strategies. For metastatic uveal melanoma (a rare melanoma of the eye), available immunotherapies are less effective, and there is currently no approved therapy for these patients. To be able to study immunotherapies in mice, we in Paper I developed an immune-humanized mouse model called patient-derived xenograft (PDX) version 2 (PDXv2). In this model, tumor cells and tumor infiltrating lymphocytes (TILs) from the same patient were grafted in IL-2 transgenic NOD/SCID IL2 receptor gamma knockout (NOG) mice, and we found that responses in the mouse model correlated to responses in the corresponding patients in a clinical trial of ACT. So far, no chimeric antigen receptor T cell (CAR-T) therapy is approved for use in solid tumors. In Paper II we tested the potential for CAR-T therapy in melanoma. First, we used TCGA to determine the expression in melanoma biopsies of targets for commercially available CAR-T cells. We found that HER2 is expressed in both cutaneous and uveal melanoma biopsies. HER2 CAR-T cells were then used to treat skin melanoma and uveal melanoma patient-derived xenografts in the PDXv2 mouse model resulting in curative responses, even in models resistant to TIL therapy. However, CAR-T cells were only effective in IL-2 transgenic mice and not in regular NOG mice. In order to facilitate translation of the findings from Paper II into a treatment strategy for patients with melanoma, we developed CAR-expressing autologous TILs (called CAR-TILs). In Paper III, we demonstrate that this strategy could overcome resistance to treatment with autologous TILs in melanoma. Current CAR-T therapies use blood-derived T cells as a substrate for CAR-T cell production. We hypothesized that by using TILs instead, we might facilitate homing to the tumor and potentially also utilize the fact that some TILs can recognize melanoma antigens, enabling a dual targeting of CAR-TILs. We also developed an automated production protocol for TILs and CAR-TILs utilizing a bioreactor, enabling safe and less variable production of the drug product.
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| 8. |
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| 9. |
- Forsberg, Elin, et al.
(författare)
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Treatment with Anti-HER2 Chimeric Antigen Receptor Tumor-Infiltrating Lymphocytes (CAR-TILs) Is Safe and Associated with Antitumor Efficacy in Mice and Companion Dogs
- 2023
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary CAR-T cells are immune cells equipped with a claw that enable them to bind cancer cells. Usually, CAR-T cells are made using immune cells from blood. Here, we tested the hypothesis that also immune cells that reside in the tumor, so called tumor-infiltrating lymphocytes, can also be modified to carry the claw. This may mean that these cells, called CAR-TILs, will be able to attack cancer cells in two ways, using the claw or binding using its normal protein on the cell surface, the so-called T cell receptor. We show that CAR-TILs can be generated, and that they can kill melanoma cells in cell culture and in mice. Finally, to prepare for clinical trials, we also assess if CAR-TILs can be safe in a human cancer patient-like model, a companion dog suffering from cancer. Our data suggest that CAR-TILs may be a way to treat patients with melanoma but human clinical trials are needed. Patients with metastatic melanoma have a historically poor prognosis, but recent advances in treatment options, including targeted therapy and immunotherapy, have drastically improved the outcomes for some of these patients. However, not all patients respond to available treatments, and around 50% of patients with metastatic cutaneous melanoma and almost all patients with metastases of uveal melanoma die of their disease. Thus, there is a need for novel treatment strategies for patients with melanoma that do not benefit from the available therapies. Chimeric antigen receptor-expressing T (CAR-T) cells are largely unexplored in melanoma. Traditionally, CAR-T cells have been produced by transducing blood-derived T cells with a virus expressing CAR. However, tumor-infiltrating lymphocytes (TILs) can also be engineered to express CAR, and such CAR-TILs could be dual-targeting. To this end, tumor samples and autologous TILs from metastasized human uveal and cutaneous melanoma were expanded in vitro and transduced with a lentiviral vector encoding an anti-HER2 CAR construct. When infused into patient-derived xenograft (PDX) mouse models carrying autologous tumors, CAR-TILs were able to eradicate melanoma, even in the absence of antigen presentation by HLA. To advance this concept to the clinic and assess its safety in an immune-competent and human-patient-like setting, we treated four companion dogs with autologous anti-HER2 CAR-TILs. We found that these cells were tolerable and showed signs of anti-tumor activity. Taken together, CAR-TIL therapy is a promising avenue for broadening the tumor-targeting capacity of TILs in patients with checkpoint immunotherapy-resistant melanoma.
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| 10. |
- Hjortsberg, Erik, et al.
(författare)
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X-ray microtomography for characterisation of cracks in iron ore pellets after reduction
- 2013
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Ingår i: Ironmaking & steelmaking. - 0301-9233 .- 1743-2812. ; 40:6, s. 399-406
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Tidskriftsartikel (refereegranskat)abstract
- This work presents a method, based on X-ray microtomography and three-dimensional (3D) image analysis, of characterising and quantifying crack distribution in iron ore pellets. The aims have been to verify the method and to determine to what extent crack propagation contributes to the decrease in compressive strength that occurs during reduction at 500°C as haematite transforms into magnetite. Raw materials known to cause disintegration problems were selected in order to promote crack propagation. Pellets displayed crack lengths of sizes roughly corresponding to half the pellet diameter already before reduction and, during reduction, a further crack propagation of ∼50% occurred. Through estimations by finite element analysis of the crack size and the pellet geometry, it has been possible to determine that this crack growth most likely is a mechanism that contributes to the decrease in compressive strength. The decrease of ∼90% that was experimentally determined to occur after 30 min of reduction is, however, too large to be explained by crack propagation alone. The study shows that the proposed techniques allow 3D imaging of iron ore pellets and characterisation of cracks. The scans are non-destructive and can be carried out repeatedly, which allows a specific sample to be studied at different stages during a process. Through future use of the proposed method, our aim is to reach a deeper understanding of the mechanisms behind low temperature disintegration of iron ore pellets and the performance of LKAB olivine pellets inside the blast furnace.
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