| 1. |
- Gerbitz, Armin, et al.
(författare)
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Prevention of CMV/EBV reactivation by double-specific T cells in patients after allogeneic stem cell transplantation : results from the randomized phase I/IIa MULTIVIR-01 study
- 2023
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionAllogeneic stem cell transplantation is used to cure hematologic malignancies or deficiencies of the hematopoietic system. It is associated with severe immunodeficiency of the host early after transplant and therefore early reactivation of latent herpesviruses such as CMV and EBV within the first 100 days are frequent. Small studies and case series indicated that application of herpes virus specific T cells can control and prevent disease in this patient population.MethodsWe report the results of a randomized controlled multi centre phase I/IIa study (MULTIVIR-01) using a newly developed T cell product with specificity for CMV and EBV derived from the allogeneic stem cell grafts used for transplantation. The study aimed at prevention and preemptive treatment of both viruses in patients after allogeneic stem cell transplantation targeting first infusion on day +30. Primary endpoints were acute transfusion reaction and acute-graft versus-host-disease after infusion of activated T cells.ResultsThirty-three patients were screened and 9 patients were treated with a total of 25 doses of the T cell product. We show that central manufacturing can be achieved successfully under study conditions and the product can be applied without major side effects. Overall survival, transplant related mortality, cumulative incidence of graft versus host disease and number of severe adverse events were not different between treatment and control groups. Expansion of CMV/EBV specific T cells was observed in a fraction of patients, but overall there was no difference in virus reactivation.DiscussionOur study results indicate peptide stimulated epitope specific T cells derived from stem cell grafts can be administered safely for prevention and preemptive treatment of reactivation without evidence for induction of acute graft versus host disease.Clinical trial registrationhttps://clinicaltrials.gov, identifier NCT02227641.
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| 2. |
- Schmittner, Andreas, et al.
(författare)
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Calibration of the carbon isotope composition (δ13C) of benthic foraminifera
- 2017
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Ingår i: Paleoceanography. - 0883-8305. ; 32:6, s. 512-530
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Tidskriftsartikel (refereegranskat)abstract
- The carbon isotope composition (δ13C) of seawater provides valuable insight on ocean circulation, air-sea exchange, the biological pump, and the global carbon cycle and is reflected by the δ13C of foraminifera tests. Here more than 1700 δ13C observations of the benthic foraminifera genus Cibicides from late Holocene sediments (δ13CCibnat) are compiled and compared with newly updated estimates of the natural (preindustrial) water column δ13C of dissolved inorganic carbon (δ13CDICnat) as part of the international Ocean Circulation and Carbon Cycling (OC3) project. Using selection criteria based on the spatial distance between samples, we find high correlation between δ13CCibnat and δ13CDICnat, confirming earlier work. Regression analyses indicate significant carbonate ion (-2.6 ± 0.4) × 10-3‰/(μmol kg-1) [CO3 2-] and pressure (-4.9 ± 1.7) × 10-3‰ m-1 (depth) effects, which we use to propose a new global calibration for predicting δ13CDICnat from δ13CCibnat. This calibration is shown to remove some systematic regional biases and decrease errors compared with the one-to-one relationship (δ13CDICnat = δ13CCibnat). However, these effects and the error reductions are relatively small, which suggests that most conclusions from previous studies using a one-to-one relationship remain robust. The remaining standard error of the regression is generally σ ≅ 0.25‰, with larger values found in the southeast Atlantic and Antarctic (σ ≅ 0.4‰) and for species other than Cibicides wuellerstorfi. Discussion of species effects and possible sources of the remaining errors may aid future attempts to improve the use of the benthic δ13C record.
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| 3. |
- Filipsson, Helena L., et al.
(författare)
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Seasonal variability of stable carbon isotopes (δ13CDIC) in the Skagerrak and the Baltic Sea : Distinguishing between mixing and biological productivity
- 2017
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Ingår i: Palaeogeography, Palaeoclimatology, Palaeoecology. - : Elsevier BV. - 0031-0182. ; 483, s. 15-30
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Tidskriftsartikel (refereegranskat)abstract
- We documented the annual cycle of the carbon isotopic composition of dissolved inorganic carbon (δ13CDIC) in the water columns of the Skagerrak and Baltic Sea to obtain an increased understanding of the processes involved controlling the carbon isotopic distribution in shelf seas. The lowest δ13CDIC values (-4.9‰) were found in the low-oxygen, brackish Baltic bottom water whereas the highest values (+1.8‰) were observed in the surface water of the Skagerrak during late summer. Photosynthesis drove the high δ13CDIC values (between 1.0 and 1.8‰) noted in the surface waters of both the Skagerrak and the Baltic. The δ13CDIC values below the halocline in the Baltic reflect mixing of brackish water and the more saline water from the Skagerrak, and foremost organic matter remineralization processes that release significant amounts of low-δ13C CO2. Similarly, in the stagnant fjord basins, little deep water exchange and the degradation of terrestrial and marine organic matter set the δ13C composition. Deep-water renewal in the fjord basins resulted in rapid increases of the δ13CDIC on the order of 1‰, whereas remineralization processes caused a decrease in δ13CDIC of 0.1-0.3‰ per month depending on location. The combined effects of water mixing and remineralization processes (estimated using apparent oxygen utilization (AOU) values) yielded the expression: δ13CDIC =0.032*S-0.01*AOU-0.12 for the Baltic - Skagerrak region at water depths below the halocline.
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| 4. |
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| 5. |
- Greco, Raffaella, et al.
(författare)
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Innovative cellular therapies for autoimmune diseases : expert-based position statement and clinical practice recommendations from the EBMT practice harmonization and guidelines committee
- 2024
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Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 69
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune diseases (ADs) are characterized by loss of immune tolerance, high chronicity, with substantial morbidity and mortality, despite conventional immunosuppression (IS) or targeted disease modifying therapies (DMTs), which usually require repeated administration. Recently, novel cellular therapies (CT), including mesenchymal stromal cells (MSC), Chimeric Antigen Receptors T cells (CART) and regulatory T cells (Tregs), have been successfully adopted in ADs. An international expert panel of the European Society for Blood and Marrow Transplantation and the International Society for the Cell and Gene Therapy, reviewed all available evidence, based on the current literature and expert practices, on use of MSC, CART and Tregs, in AD patients with rheumatological, neurological, and gastroenterological indications. Expert -based consensus and recommendations for best practice and quality of patient care were developed to support clinicians, scientists, and their multidisciplinary teams, as well as patients and care providers and will be regularly updated. Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 6. |
- Zippelius, Alfred, et al.
(författare)
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Effector function of human tumor-specific CD8 T cells in melanoma lesions : a state of local functional tolerance.
- 2004
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 64:8, s. 2865-73
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Tidskriftsartikel (refereegranskat)abstract
- Although tumor-specific CD8 T-cell responses often develop in cancer patients, they rarely result in tumor eradication. We aimed at studying directly the functional efficacy of tumor-specific CD8 T cells at the site of immune attack. Tumor lesions in lymphoid and nonlymphoid tissues (metastatic lymph nodes and soft tissue/visceral metastases, respectively) were collected from stage III/IV melanoma patients and investigated for the presence and function of CD8 T cells specific for the tumor differentiation antigen Melan-A/MART-1. Comparative analysis was conducted with peripheral blood T cells. We provide evidence that in vivo-priming selects, within the available naive Melan-A/MART-1-specific CD8 T-cell repertoire, cells with high T-cell receptor avidity that can efficiently kill melanoma cells in vitro. In vivo, primed Melan-A/MART-1-specific CD8 T cells accumulate at high frequency in both lymphoid and nonlymphoid tumor lesions. Unexpectedly, however, whereas primed Melan-A/MART-1-specific CD8 T cells that circulate in the blood display robust inflammatory and cytotoxic functions, those that reside in tumor lesions (particularly in metastatic lymph nodes) are functionally tolerant. We show that both the lymph node and the tumor environments blunt T-cell effector functions and offer a rationale for the failure of tumor-specific responses to effectively counter tumor progression.
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