| 1. |
- Säll, Anna, et al.
(författare)
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Generation and analyses of human synthetic antibody libraries and their application for protein microarrays
- 2016
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Ingår i: Protein Engineering Design & Selection. - : Oxford University Press. - 1741-0126 .- 1741-0134. ; 29:10, s. 427-437
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Tidskriftsartikel (refereegranskat)abstract
- Antibody-based proteomics offers distinct advantages in the analysis of complex samples for discovery and validation of biomarkers associated with disease. However, its large-scale implementation requires tools and technologies that allow development of suitable antibody or antibody fragments in a high-throughput manner. To address this we designed and constructed two human synthetic antibody fragment (scFv) libraries denoted HelL-11 and HelL-13. By the use of phage display technology, in total 466 unique scFv antibodies specific for 114 different antigens were generated. The specificities of these antibodies were analyzed in a variety of immunochemical assays and a subset was further evaluated for functionality in protein microarray applications. This high-throughput approach demonstrates the ability to rapidly generate a wealth of reagents not only for proteome research, but potentially also for diagnostics and therapeutics. In addition, this work provides a great example on how a synthetic approach can be used to optimize library designs. By having precise control of the diversity introduced into the antigen-binding sites, synthetic libraries offer increased understanding of how different diversity contributes to antibody binding reactivity and stability, thereby providing the key to future library optimization.
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| 2. |
- Andersson, Eva, et al.
(författare)
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CD4+CD57+ T cells derived from peripheral blood do not support immunoglobulin production by B cells
- 1995
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Ingår i: Cellular Immunology. - : Elsevier BV. - 0008-8749. ; 163:2, s. 245-253
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Tidskriftsartikel (refereegranskat)abstract
- A small subpopulation of CD4+ T cells found in peripheral blood coexpresses the CD57+ marker normally found on, e.g., NK cells. It is known that this population occurs in a higher frequency in certain diseases. The same antigen has also been shown to be expressed on CD4+ T cells derived from germinal centers. The localization of this cell population to specialized lymphoid structures suggests that it may play a role in the evolution of the antibody response following antigenic stimulation in vivo. We have examined the ability of peripheral blood helper T cells coexpressing CD57 to participate in B cell activation/differentiation and evaluated their responses to polyclonal stimulation. The CD4+CD57+ T cells do not express mRNA for a number of different cytokines or for the CD40 ligand after activation in vitro. Furthermore these cells do not induce differentiation of B cells into immunoglobulin-producing cells. Consequently, despite their CD4 phenotype and their ability to be activated, to express the IL-2 receptor, and to enter into the cell cycle, they do not act as T helper cells under conditions where CD4+/CD57- cells normally do so. The findings suggest that this peripheral blood helper T cell population is functionally different from regular CD4+ T cells. The basis for the lack of proper costimulatory signals for immunoglobulin production might be related to the low expression of CD28.
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| 3. |
- Andersson, Eva, et al.
(författare)
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Immunoglobulin production induced by CD57+ GC-derived helper T cells in vitro requires addition of exogenous IL-2
- 1996
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Ingår i: Cellular Immunology. - : Elsevier BV. - 0008-8749. ; 169:2, s. 166-173
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Tidskriftsartikel (refereegranskat)abstract
- Germinal centers (GC) are well-defined areas in lymphoid organs were B cells proliferate and differentiate in response to T-cell-dependent antigens. The GC comprises B cells, follicular dendritic cells, tangible body macrophages, and a low number of CD4+ T cells. A large portion of these T cells expresses CD57. We have examined the ability of the CD4+CD57+ GC T cells to become activated and to take part in B cell activation processes, These T cells coexpress CD45RO, CD69, CD28, and upon mitogenic stimulation CD25, The cell population was found neither to containe nor to be able to produce any specific mRNA for IL-2, IL-4, and IFN-γ upon activation. Levels of mRNA encoding CD40 ligand was also undetectable under similar conditions. Furthermore, in contrast to ordinary CD4+ T cells, this population expressing CD57 was unable to induce B cells to Ig production in the presence of pokeweed mitogen or SEA unless IL-2 was added to the cultures, However, despite their apparent lack of function CD4+CD57+ GC T cells were found to rescue GC B cells from cell death in vitro to the same extent as CD4+CD57- T(h) cells, The phenotypical and functional differences found between these T cells and regular T(h)-cells suggest that they either represent a T cell subset with distinct properties within the GC yet to be determined or that they represent T cells, Irate in the immune response, having lost most of their original functions and capabilities.
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| 4. |
- Andreasson, Ulrika, et al.
(författare)
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B cell lymphomas express CX(3)CR1 a non-B cell lineage adhesion molecule
- 2008
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Ingår i: Cancer Letters. - : Elsevier BV. - 0304-3835 .- 1872-7980. ; 259:2, s. 138-145
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Tidskriftsartikel (refereegranskat)abstract
- To study the differential expression of cell membrane-bound receptors and their potential role in growth and/or survival of the tumor cells, highly purified follicular lymphoma cells were analyzed, using gene expression analysis, and compared to non-malignant B cell populations. Filtering the genome for overexpressed genes coding for cell membrane-bound proteins/receptors resulted in a hit list of 27 identified genes. Among these, we have focused on the aberrant over expression of CX3CR1, in different types of B cell lymphoma, as compared to non-malignant B cells. We show that CX3CR1, which normally is not expressed on B cells, is expressed both at the mRNA and protein level in several subtypes of lymphoma. CX3CR1 has also shown to be involved in the homing to specific tissues that express the ligand, CX3CL1, in breast and prostate cancer and may thus be involved in dissemination of lymphoma.
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| 5. |
- Axelsson, Ulrika, et al.
(författare)
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A multicenter study investigating the molecular fingerprint of psychological resilience in breast cancer patients : Study protocol of the SCAN-B resilience study
- 2018
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Individual patients differ in their psychological response when receiving a cancer diagnosis, in this case breast cancer. Given the same disease burden, some patients master the situation well, while others experience a great deal of stress, depression and lowered quality of life. Patients with high psychological resilience are likely to experience fewer stress reactions and better adapt to and manage the life threat and the demanding treatment that follows the diagnosis. If this phenomenon of mastering difficult situations is reflected also in biomolecular processes is not much studied, nor has its capacity for impacting the cancer prognosis been addressed. This project specifically aims, for the first time, to investigate how a breast cancer patient's psychological resilience is coupled to biomolecular parameters using advanced "omics" and, as a secondary aim, whether it relates to prognosis and quality of life one year after diagnosis. Method: The study population consists of newly diagnosed breast cancer patients enrolled in the Sweden Cancerome Analysis Network - Breast (SCAN-B) at four hospitals in Sweden. At the time of cancer diagnosis, the patient fills out the standardized method to measure psychological resilience, the "Connor-Davidson Resilience scale" (CD-RISC), the quality of life measure SF-36, as well as providing social and socioeconomic variables. In addition, one blood sample is collected. At the one-year follow-up, the patient will be subjected to the same assessments, and we also collect information regarding smoking, exercise habits, and BMI, as well as patients' trust in the treatment and their satisfaction with the care and treatment. Discussion: This explorative hypothesis-generating project will pave the way for larger validation studies, potentially leading to a standardized method of measuring psychological resilience as an important parameter in cancer care. Revealing the body-mind interaction, in terms of psychological resilience and quality of life, will herald the development of truly personalized psychosocial care and cancer intervention treatment strategies. Trial registration: This is a retrospectively registered trial at ClinicalTrials.gov, ID: NCT03430492on February 6, 2018.
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| 6. |
- Barreveld, Antje M., et al.
(författare)
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An artificial intelligence-powered, patient-centric digital tool for self-management of chronic pain : a prospective, multicenter clinical trial
- 2023
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Ingår i: Pain Medicine (United States). - 1526-2375. ; 24:9, s. 1100-1110
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate how a behavioral health, artificial intelligence (AI)-powered, digital self-management tool affects the daily functions in adults with chronic back and neck pain. Design: Eligible subjects were enrolled in a 12-week prospective, multicenter, single-arm, open-label study and instructed to use the digital coach daily. Primary outcome was a change in Patient-Reported Outcomes Measurement Information Systems (PROMIS) scores for pain interference. Secondary outcomes were changes in PROMIS physical function, anxiety, depression, pain intensity scores and pain catastrophizing scale (PCS) scores. Methods: Subjects logged daily activities, using PainDrainerTM, and data analyzed by the AI engine. Questionnaire and web-based data were collected at 6 and 12 weeks and compared to subjects' baseline. Results: Subjects completed the 6- (n = 41) and 12-week (n = 34) questionnaires. A statistically significant Minimal Important Difference (MID) for pain interference was demonstrated in 57.5% of the subjects. Similarly, MID for physical function was demonstrated in 72.5% of the subjects. A pre- to post-intervention improvement in depression score was also statistically significant, observed in 100% of subjects, as was the improvement in anxiety scores, evident in 81.3% of the subjects. PCS mean scores was also significantly decreased at 12 weeks. Conclusion: Chronic pain self-management, using an AI-powered, digital coach anchored in behavioral health principles significantly improved subjects' pain interference, physical function, depression, anxiety, and pain catastrophizing over the 12-week study period.
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| 7. |
- Borrebaeck, Carl A K, et al.
(författare)
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Does endogenous glycosylation prevent the use of mouse monoclonal antibodies as cancer therapeutics?
- 1993
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Ingår i: Immunology Today. - 0167-5699. ; 14:10, s. 477-479
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Tidskriftsartikel (refereegranskat)abstract
- Monoclonal antibodies have many potential therapeutic benefits. However, when applied to humans, mouse monoclonal antibodies have several disadvantages. Here Carl Borrebaeck and colleagues describe a strategy to overcome the anti-Gal activity, thought to be one of the reasons why mouse mAbs have a limited half-life.
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| 8. |
- Borrebaeck, Carl A K, et al.
(författare)
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Kinetic analysis of recombinant antibody-antigen interactions : Relation between structural domains and antigen binding
- 1992
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Ingår i: Bio/Technology. - : Springer Science and Business Media LLC. - 0733-222X. ; 10:6, s. 697-698
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Tidskriftsartikel (refereegranskat)abstract
- The relation between domain structures of recombinant monoclonal antibody fragments and their reaction kinetics was studied for the first time using a novel biosensor based on surface plasmon resonance technology. The association and dissociation rate constants of Fab, Fv and single domain (VH fragment) anti-lysozyme antibodies were determined and compared to the intact monoclonal antibody. Fab and Fv fragments showed similar reaction kinetics and had affinity constants of 6 X 109 M-1 and 25 X 109 M-1, respectively. The single domain antibody had significantly different reaction kinetics compared to the fragments consisting of paired heavy and light chain domains. The VH domain had both a higher dissociation and a lower association rate constant, which resulted in an affinity constant approximately 250 times lower than the Fab fragment. This rapid evaluation of antibody reaction kinetics should prove to be an important selection parameter when comparing antibody fragments for their utility in therapeutic or other applications.
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| 9. |
- Borrebaeck, Carl A K
(författare)
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Precision diagnostics : moving towards protein biomarker signatures of clinical utility in cancer
- 2017
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Ingår i: Nature Reviews Cancer. - : Springer Science and Business Media LLC. - 1474-175X .- 1474-1768. ; 17:3, s. 199-204
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Forskningsöversikt (refereegranskat)abstract
- Interest in precision diagnostics has been fuelled by the concept that early detection of cancer would benefit patients; that is, if detected early, more tumours should be resectable and treatment more efficacious. Serum contains massive amounts of potentially diagnostic information, and affinity proteomics has risen as an accurate approach to decipher this, to generate actionable information that should result in more precise and evidence-based options to manage cancer. To achieve this, we need to move from single to multiplex biomarkers, a so-called signature, that can provide significantly increased diagnostic accuracy. This Opinion article focuses on the progress being made in identifying protein biomarker signatures of clinical utility, using blood-based proteomics.
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| 10. |
- Borrebaeck, Carl A K, et al.
(författare)
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Recombinant Antibody Microarray for Profiling the Serum Proteome of SLE.
- 2014
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Ingår i: Methods in Molecular Biology. - New York, NY : Springer New York. - 1940-6029. ; 1134, s. 67-78
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is a severe autoimmune connective tissue disease. Our current knowledge about the serum proteome, or serum biomarker panels, reflecting disease and disease status is still very limited. Affinity proteomics, represented by recombinant antibody arrays, is a novel, multiplex technology for high-throughput protein expression profiling of crude serum proteomes in a highly specific, sensitive, and miniaturized manner. The antibodies are deposited one by one in an ordered pattern, an array, onto a solid support. Next, the sample is added, and any specifically bound proteins are detected and quantified. The binding pattern is then converted into a relative protein expression map, or protein map, deciphering the composition of the sample at the molecular level. The methodology provides unique opportunities for delineating serum biomarkers reflecting SLE, thus paving the way for improved diagnosis, classification, and prognosis.
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