| 1. |
- Ellmark, Peter, et al.
(författare)
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Modulation of the CD40-CD40 ligand interaction using human anti-CD40 single-chain antibody fragments obtained from the n-CoDeR phage display library
- 2002
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Ingår i: Immunology. - 0019-2805. ; 106:4, s. 456-463
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Tidskriftsartikel (refereegranskat)abstract
- CD40 plays a central regulatory role in the immune system and antibodies able to modulate CD40 signalling may consequently have a potential in immunotherapy, in particular for treatment of lymphomas and autoimmune disease like multiple sclerosis. As a first step to achieve this goal, we describe the selection and characterization of a novel set of fully human anti-CD40 antibody fragments (scFv) from a phage display library (n-CoDeR). In order to determine their biological potential, these antibody fragments have been analysed for their ability to promote B-cell activation, rescue from apoptosis and to block the CD40-CD40 ligand (CD40L) interaction. The selected cohort of human scFv could be subcategorized, each expressing a distinct functional signature. Thus scFv were generated that induced B-cell proliferation, rescued B cells from apoptosis and blocked the CD40-CD40L interaction to different extents. In particular, one of the scFv clones (F33) had the ability to abrogate completely this interaction. The epitope recognition patterns as well as individual rate constants were also determined and the affinity was shown to vary from low to high nanomolar range. In conclusion, this panel of human anti-CD40 scFv fragments displays a number of distinct properties, which may constitute a valuable source when evaluating candidates for in vivo trials.
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| 2. |
- Lundbäck, Peter, et al.
(författare)
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A novel high mobility group box 1 neutralizing chimeric antibody attenuates drug-induced liver injury and postinjury inflammation in mice
- 2016
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 64:5, s. 1699-1710
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Tidskriftsartikel (refereegranskat)abstract
- Acetaminophen (APAP) overdoses are of major clinical concern. Growing evidence underlines a pathogenic contribution of sterile postinjury inflammation in APAP-induced acute liver injury (APAP-ALI) and justifies development of anti-inflammatory therapies with therapeutic efficacy beyond the therapeutic window of the only current treatment option, N-acetylcysteine (NAC). The inflammatory mediator, high mobility group box 1 (HMGB1), is a key regulator of a range of liver injury conditions and is elevated in clinical and preclinical APAP-ALI. The anti-HMGB1 antibody (m2G7) is therapeutically beneficial in multiple inflammatory conditions, and anti-HMGB1 polyclonal antibody treatment improves survival in a model of APAP-ALI. Herein, we developed and investigated the therapeutic efficacy of a partly humanized anti-HMGB1 monoclonal antibody (mAb; h2G7) and identified its mechanism of action in preclinical APAP-ALI. The mouse anti-HMGB1 mAb (m2G7) was partly humanized (h2G7) by merging variable domains of m2G7 with human antibody-Fc backbones. Effector function-deficient variants of h2G7 were assessed in comparison with h2G7 in vitro and in preclinical APAP-ALI. h2G7 retained identical antigen specificity and comparable affinity as m2G7. 2G7 treatments significantly attenuated APAP-induced serum elevations of alanine aminotransferase and microRNA-122 and completely abrogated markers of APAP-induced inflammation (tumor necrosis factor, monocyte chemoattractant protein 1, and chemokine [C-X-C motif] ligand 1) with prolonged therapeutic efficacy as compared to NAC. Removal of complement and/or Fc receptor binding did not affect h2G7 efficacy. Conclusion: This is the first report describing the generation of a partly humanized HMGB1-neutralizing antibody with validated therapeutic efficacy and with a prolonged therapeutic window, as compared to NAC, in APAP-ALI. The therapeutic effect was mediated by HMGB1 neutralization and attenuation of postinjury inflammation. These results represent important progress toward clinical implementation of HMGB1-specific therapy as a means to treat APAP-ALI and other inflammatory conditions. (Hepatology 2016;64:1699-1710).
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| 3. |
- Ottosson, Camilla, et al.
(författare)
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Early integration of the user’s perspective in the renovation process: Experiences from an “In-depth Dialogue Process with Residents” in rental flats from the 1950s
- 2014
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Ingår i: World Sustainable Building Congress Barcelona 28-30 October 2014.
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Konferensbidrag (refereegranskat)abstract
- An “In-depth dialogue with residents” has been applied in the pre-study of a renovation of a housing area from 1950s with about 500 rental flats. The paper presents the result from this dialogue process and discusses the potential of the methodology to achieve a more integrated, sustainable renovation. The process was carried out by a transdisciplinary team with representatives from the housing manager, an architect firm with competences in sociology, the tenant organization, and researchers from architecture and environmental psychology. The dialogue process comprised four main activities: design of process and selection of tools, data collection, compilation of material and feedback to residents and housing company, and a following-up. Data about the residents view were collected by intercept interviews, a questionnaire survey, a walking tour, and a focus group interview. The dialogue process identified values appreciated by the residents and had impact on alternative renovation option for the flats.
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| 4. |
- Ottosson, Camilla, et al.
(författare)
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Fördjupad boendedialog Långängen, Göteborg
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Under perioden maj 2012 till juni 2013 genomfördes en fördjupad boendedialogi Familjebostäders bestånd i området Långängen i Göteborg. Området består avflerbostadshus byggda i början av 1950-talet. Syftet med den fördjupade boendedialogenär att medvetandegöra och bygga konsensus kring behovet och genomförandet av enstörre renovering. I dialogprocessen ingår en rad aktiviteter och projektspecifika data harsamlats in från dagens boende genom en nulägesbeskrivning, genskjutsintervjuer, enenkätundersökning, en gå-tur, och en fokusgruppsintervju. Nulägesbeskrivningen beskriverområdet och befolkningens sammansättning utifrån statistik och genomförda studier medfokus på sociala aspekter. Genskjutsintervjuer, som är kortare former av intervjuer, ger enöversiktlig bild av de yttre boendekvaliteterna. Enkätundersökningen visar hyresgästers synpå sin bostad, sitt område och deras inställning och tankar kring framtida renoveringar. Gåturen,en metod för utvärdering av valda platser med boende och människor som arbetari den aktuella miljön på plats samtidigt, identifierar platsernas utvecklingsmöjligheter.Fokusgruppsintervjun ger en fördjupad förståelse för de yngre boendes syn på sittområde och behovet att förnyelse och bevarande. Resultaten från undersökningarnahar återkopplats löpande till Familjebostäder och på ett återkopplingsmöte till boende.Processen pågår och dialogen fortsätter i form av referensgrupper.“Fördjupat boendedialog i Långängen, Göteborg” är också ett delprojekt inomforskningsprojektet Rebo – Strategier för integrerat hållbar renovering av bostadsbestånd –Fokus på perioden ‘folkhemmet’.
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