Krasimira Aleksandrova
Hannover Medical School
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Publication
Featured researches published by Krasimira Aleksandrova.
Journal of Hepatology | 2008
Lutz Schwettmann; Michael Wehmeier; Dunja Jokovic; Krasimira Aleksandrova; Korbinian Brand; Michael P. Manns; Ralf Lichtinghagen; Matthias J. Bahr
BACKGROUND/AIMS ADAMs (A Disintegrin And Metalloprotease) are multifunctional, membrane-bound and soluble cell surface glycoproteins with numerous functions in cell physiology. We assessed the expression of ADAMs in fibrotic liver disease of different aetiologies and clarified whether the expression of ADAMs is related to histological staging of fibrosis. In addition, the expression of ADAMs was determined in different cell types of liver. METHODS Seventy-one biopsy samples from patients with chronic liver diseases were analyzed for mRNA expression of ADAM-8, -9, -12, -28, -TS1, -TS2, matrix metalloprotease (MMP)-2, -9 and tissue inhibitor of metalloproteinases-1 and -2 by quantitative real-time RT-PCR. RESULTS The ADAM expression in liver injury is independent of aetiology. A strong correlation between ADAM -9, -28, -TS1 versus MMP-2 and SMA was identified. Activated hepatic stellate cells (HSC) showed increased mRNA expression of ADAM-8, -9, -12, -28, -TS2 compared to quiescent HSC. Significant differences between histological stages of fibrosis were found for ADAM-28, MMP-2 and MMP-9. CONCLUSIONS The results suggest that ADAMs are differentially expressed in the liver. We assume that ADAM-9, -TS1 and -TS2 play a crucial role in extracellular matrix remodeling during fibrotic processes in the liver.
Human Gene Therapy | 2016
Christoph Priesner; Krasimira Aleksandrova; Ruth Esser; Nadine Mockel-Tenbrinck; Jana Leise; Katharina Drechsel; Michael Marburger; Andrea Quaiser; Lilia Goudeva; Lubomir Arseniev; Andrew Kaiser; Wolfgang Glienke; Ulrike Koehl
Multiple clinical studies have demonstrated that adaptive immunotherapy using redirected T cells against advanced cancer has led to promising results with improved patient survival. The continuously increasing interest in those advanced gene therapy medicinal products (GTMPs) leads to a manufacturing challenge regarding automation, process robustness, and cell storage. Therefore, this study addresses the proof of principle in clinical-scale selection, stimulation, transduction, and expansion of T cells using the automated closed CliniMACS® Prodigy system. Naïve and central memory T cells from apheresis products were first immunomagnetically enriched using anti-CD62L magnetic beads and further processed freshly (n = 3) or split for cryopreservation and processed after thawing (n = 1). Starting with 0.5 × 108 purified CD3+ T cells, three mock runs and one run including transduction with green fluorescent protein (GFP)-containing vector resulted in a median final cell product of 16 × 108 T cells (32-fold expansion) up to harvesting after 2 weeks. Expression of CD62L was downregulated on T cells after thawing, which led to the decision to purify CD62L+CD3+ T cells freshly with cryopreservation thereafter. Most important in the split product, a very similar expansion curve was reached comparing the overall freshly CD62L selected cells with those after thawing, which could be demonstrated in the T cell subpopulations as well by showing a nearly identical conversion of the CD4/CD8 ratio. In the GFP run, the transduction efficacy was 83%. In-process control also demonstrated sufficient glucose levels during automated feeding and medium removal. The robustness of the process and the constant quality of the final product in a closed and automated system give rise to improve harmonized manufacturing protocols for engineered T cells in future gene therapy studies.
Human Gene Therapy | 2016
Christoph Priesner; Krasimira Aleksandrova; Ruth Esser; Nadine Mockel-Tenbrinck; Leise J; Katharina Drechsel; Michael Marburger; Andrea Quaiser; Lilia Goudeva; Lubomir Arseniev; Andrew Kaiser; Wolfgang Glienke; Ulrike Koehl
Multiple clinical studies have demonstrated that adaptive immunotherapy using redirected T cells against advanced cancer has led to promising results with improved patient survival. The continuously increasing interest in those advanced gene therapy medicinal products (GTMPs) leads to a manufacturing challenge regarding automation, process robustness, and cell storage. Therefore, this study addresses the proof of principle in clinical-scale selection, stimulation, transduction, and expansion of T cells using the automated closed CliniMACS® Prodigy system. Naïve and central memory T cells from apheresis products were first immunomagnetically enriched using anti-CD62L magnetic beads and further processed freshly (n = 3) or split for cryopreservation and processed after thawing (n = 1). Starting with 0.5 × 108 purified CD3+ T cells, three mock runs and one run including transduction with green fluorescent protein (GFP)-containing vector resulted in a median final cell product of 16 × 108 T cells (32-fold expansion) up to harvesting after 2 weeks. Expression of CD62L was downregulated on T cells after thawing, which led to the decision to purify CD62L+CD3+ T cells freshly with cryopreservation thereafter. Most important in the split product, a very similar expansion curve was reached comparing the overall freshly CD62L selected cells with those after thawing, which could be demonstrated in the T cell subpopulations as well by showing a nearly identical conversion of the CD4/CD8 ratio. In the GFP run, the transduction efficacy was 83%. In-process control also demonstrated sufficient glucose levels during automated feeding and medium removal. The robustness of the process and the constant quality of the final product in a closed and automated system give rise to improve harmonized manufacturing protocols for engineered T cells in future gene therapy studies.
Frontiers in Immunology | 2016
Christoph Priesner; Ruth Esser; Sabine Tischer; Michael Marburger; Krasimira Aleksandrova; Britta Maecker-Kolhoff; Hans-Gert Heuft; Lilia Goudeva; Rainer Blasczyk; Lubomir Arseniev; Ulrike Köhl; Britta Eiz-Vesper; Stephan Klöß
Background and aims The infusion of enriched CMV-specific donor T-cells appears to be a suitable alternative for the treatment of drug-resistant CMV reactivation or de novo infection after both solid organ and hematopoietic stem cell transplantation. Antiviral lymphocytes can be selected from apheresis products using the CliniMACS Cytokine-Capture-System® either with the well-established CliniMACS® Plus (Plus) device or with its more versatile successor CliniMACS Prodigy® (Prodigy). Methods Manufacturing of CMV-specific T-cells was carried out with the Prodigy and Plus in parallel starting with 0.8–1 × 109 leukocytes collected by lymphapheresis (n = 3) and using the MACS GMP PepTivator® HCMVpp65 for antigenic restimulation. Target and non-target cells were quantified by a newly developed single-platform assessment and gating strategy using positive (CD3/CD4/CD8/CD45/IFN-γ), negative (CD14/CD19/CD56), and dead cell (7-AAD) discriminators. Results Both devices produced largely similar results for target cell viabilities: 37.2–52.2% (Prodigy) vs. 51.1–62.1% (Plus) CD45+/7-AAD− cells. Absolute numbers of isolated target cells were 0.1–3.8 × 106 viable IFN-γ+ CD3+ T-cells. The corresponding proportions of IFN-γ+ CD3+ T-cells ranged between 19.2 and 95.1% among total CD3+ T-cells and represented recoveries of 41.9–87.6%. Within two parallel processes, predominantly IFN-γ+ CD3+CD8+ cytotoxic T-cells were enriched compared to one process that yielded a higher amount of IFN-γ+ CD3+CD4+ helper T lymphocytes. T-cell purity was higher for the Prodigies products that displayed a lower content of contaminating IFN-γ− T-cells (3.6–20.8%) compared to the Plus products (19.9–80.0%). Conclusion The manufacturing process on the Prodigy saved both process and hands-on time due to its higher process integration and ability for unattended operation. Although the usage of both instruments yielded comparable results, the lower content of residual IFN-γ− T-cells in the target fractions produced with the Prodigy may allow for a higher dosage of CMV-specific donor T-cells without increasing the risk for graft-versus-host disease.
Journal of Translational Medicine | 2014
Sabine Tischer; Christoph Priesner; Hans-Gert Heuft; Lilia Goudeva; Wolfgang Mende; Marc Barthold; Stephan Kloeß; Lubomir Arseniev; Krasimira Aleksandrova; Britta Maecker-Kolhoff; Rainer Blasczyk; Ulrike Koehl; Britta Eiz-Vesper
Archive | 2011
Kimberly Ann Siems; Sonya Olabisi Amelia Meheux Sherwood; Krasimira Aleksandrova; Lubomir Arseniev
Archive | 2011
Krasimira Aleksandrova; Marc Barthold; Lubomir Arseniev; Carsten Griesel; Christoph Priesner
Archive | 2015
Krasimira Aleksandrova; Stephan Klöß; Lubomir Arseniev; Ulrike Köhl
Archive | 2011
Krasimira Aleksandrova; Marc Barthold; Lubomir Arseniev; Carsten Griesel; Christoph Priesner
Archive | 2010
Krasimira Aleksandrova; Marc Barthold; Lubomir Arseniev; Carsten Griesel; Christoph Priesner