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1. Outcomes of haploidentical transplants with PT-CY vs 10/10 MUD transplants with ATG in Germany

Author

Kröger, Nicolaus, Schroeder, Thomas, Stelljes, Matthias, Dreger, Peter, Zeiser, Robert, Bethge, Wolfgang, Teschner, Daniel, Edinger, Matthias, Platzbecker, Uwe, Elmaagacli, Ahmet, Hilgendorf, Inken, Burchert, Andreas, Stölzel, Friedrich, Verbeek, Mareike, Sala, Elisa, Tischer, Johanna, Schetelig, Johannes, Brecht, Arne, Kaufmann, Martin, Kimmich, Christoph, Bittenbring, Jörg Thomas, Wulf, Gerald, Blau, Igor Wolfgang, Winkler, Julia, Bug, Gesine, Jost, Edgar, Holderried, Tobias, Dürholt, Mareike, Scheid, Christof, Wagner-Drouet, Eva, Wolleschak, Denise, Ringhoffer, Mark, Kiehl, Michael, Wortmann, Friederike, Kobbe, Guido, Schroers, Roland, Krackhardt, Angela, Klein, Stefan, Müller, Lutz P., Schmid, Christoph, Kaun, Stephan, Wieschermann, Ute, Bartscht, Tobias, Meyer, Ralf Georg, Wölfl, Matthias, Bader, Peter, Niederland, Judith, Maucher, Jakob, Mauz-Körholz, Christine, Burkhardt, Birgit, Kentouche, Karim, Passweg, Jakob, Ehlert, Karoline, Arslan, Aysenur, Labuhn, Svenja, Schröder, Thomas, Franke, Georg-Nikolaus, Eder, Matthias, Amann, Elisa Maria, Neuchel, Christine, Schmid-Möglich, Amelie, Schmeller, Sandra, Beyersmann, Jan, Schrezenmeier, Hubert, Mytilineos, Joannis, and Fürst, Daniel

Published
2024
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2. Autoantibody mediated deficiency of IL-36-receptor antagonist in a subset of patients with psoriasis and psoriatic arthritis

Author

Hoffmann, Marie-Christin, Fadle, Natalie, Regitz, Evi, Kos, Igor Age, Cetin, Onur, Lesan, Vadim, Preuss, Klaus-Dieter, Zaks, Marina, Stöger, Elisabeth, Zimmer, Vincent, Klemm, Philipp, Assmann, Gunter, Pfeifer, Jochen, Bittenbring, Joerg Thomas, Bewarder, Moritz, Vogt, Thomas, Pföhler, Claudia, Thurner, Bernhard, Kessel, Christoph, and Thurner, Lorenz

Published
2024
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3. Autoantibody-Mediated Depletion of IL-1RA in Still’s Disease and Potential Impact of IL-1 Targeting Therapies

Author

Hoffmann, Marie-Christin, Cavalli, Giulio, Fadle, Natalie, Cantoni, Eleonora, Regitz, Evi, Fleser, Octavian, Klemm, Philipp, Zaks, Marina, Stöger, Elisabeth, Campochiaro, Corrado, Tomelleri, Alessandro, Baldissera, Elena, Bittenbring, Jörg Thomas, Zimmer, Vincent, Pfeifer, Jochen, Fischer, Yvan, Preuss, Klaus-Dieter, Bewarder, Moritz, Thurner, Bernhard, Fuehner, Sabrina, Foell, Dirk, Dagna, Lorenzo, Kessel, Christoph, and Thurner, Lorenz

Published
2024
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6. KIR2DS1–HLA-C status as a predictive marker for benefit from rituximab: a post-hoc analysis of the RICOVER-60 and CLL8 trials

Author

Kaddu-Mulindwa, Dominic, Altmann, Bettina, Robrecht, Sandra, Ziepert, Marita, Regitz, Evi, Tausch, Eugen, Held, Gerhard, Poeschel, Viola, Lesan, Vadim, Bittenbring, Joerg Thomas, Thurner, Lorenz, Pfreundschuh, Michael, Christofyllakis, Konstantinos, Truemper, Lorenz, Loeffler, Markus, Schmitz, Norbert, Hoth, Markus, Hallek, Michael, Fischer, Kirsten, Stilgenbauer, Stephan, Bewarder, Moritz, and Rixecker, Torben Millard

Published
2022
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7. LRPAP1 autoantibodies in mantle cell lymphoma are associated with superior outcome

Author

Thurner, Lorenz, Fadle, Natalie, Bittenbring, Jörg Thomas, Regitz, Evi, Schuck, Rita, Cetin, Onur, Stuhr, Ariane, Rixecker, Torben, Murawski, Niels, Poeschel, Viola, Kaddu-Mulindwa, Dominic, Preuss, Klaus-Dieter, Stilgenbauer, Stephan, Hermine, Olivier, Kluin-Nelemans, Hanneke C., Hartmann, Sylvia, Dreyling, Martin, Pott, Christiane, Bewarder, Moritz, and Hoster, Eva

Published
2021
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8. Outcomes of haploidentical transplants with PT-CY vs 10/10 MUD transplants with ATG in Germany

Author

Arslan, Aysenur, Labuhn, Svenja, Sala, Elisa, Ringhoffer, Mark, Schetelig, Johannes, Schröder, Thomas, Bug, Gesine, Franke, Georg-Nikolaus, Stelljes, Matthias, Dreger, Peter, Zeiser, Robert, Teschner, Daniel, Bethge, Wolfgang, Eder, Matthias, Edinger, Matthias, Amann, Elisa Maria, Neuchel, Christine, Schmid-Möglich, Amelie, Schmeller, Sandra, Beyersmann, Jan, Schrezenmeier, Hubert, Mytilineos, Joannis, Kröger, Nicolaus, Fürst, Daniel, Kröger, Nicolaus, Schroeder, Thomas, Stelljes, Matthias, Dreger, Peter, Zeiser, Robert, Bethge, Wolfgang, Teschner, Daniel, Edinger, Matthias, Platzbecker, Uwe, Elmaagacli, Ahmet, Hilgendorf, Inken, Burchert, Andreas, Stölzel, Friedrich, Verbeek, Mareike, Sala, Elisa, Tischer, Johanna, Schetelig, Johannes, Brecht, Arne, Kaufmann, Martin, Kimmich, Christoph, Bittenbring, Jörg Thomas, Wulf, Gerald, Blau, Igor Wolfgang, Winkler, Julia, Bug, Gesine, Jost, Edgar, Holderried, Tobias, Dürholt, Mareike, Scheid, Christof, Wagner-Drouet, Eva, Wolleschak, Denise, Ringhoffer, Mark, Kiehl, Michael, Wortmann, Friederike, Kobbe, Guido, Schroers, Roland, Krackhardt, Angela, Klein, Stefan, Müller, Lutz P., Schmid, Christoph, Kaun, Stephan, Wieschermann, Ute, Bartscht, Tobias, Meyer, Ralf Georg, Wölfl, Matthias, Bader, Peter, Niederland, Judith, Maucher, Jakob, Mauz-Körholz, Christine, Burkhardt, Birgit, Kentouche, Karim, Passweg, Jakob, and Ehlert, Karoline

Abstract

•Five-year OS and DFS were significantly lower in PT-CY Haplo transplantation than 10/10 MUD transplantation with ATG in a German cohort.•10/10 MUD transplantation with ATG provides higher GRFS and lower aGVHD, cGVHD, and nonrelapse mortality (NRM) than PT-CY Haplo in a German cohort.

Published
2024
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9. Prophylactic Peripheral Blood Stem Cell Collection in Patients with Extensive Bone-Marrow Infiltration of Neuroendocrine Tumours Prior to Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE

Author

Sabet, Amir, Mader, Nicolai, Bittenbring, Jörg Thomas, Khreish, Fadi, Grünwald, Frank, Biersack, Hans-Jürgen, and Ezziddin, Samer

Subjects
peptide receptor radionuclide therapy, Communication, RS1-441, NET, Pharmacy and materia medica, peripheral blood stem cell collection, Medicine, ddc:610, PRRT, PBSC, neuroendocrine tumor, hematotoxicity
Abstract

Peptide receptor radionuclide therapy (PRRT) of metastatic neuroendocrine tumors (NET) can be successfully repeated but may eventually be dose-limited. Since 177Lu-DOTATATE dose limitation may come from hematological rather than renal function, hematological peripheral blood stem cell backup might be desirable. Here, we report our initial experience of peripheral blood stem-cell collection (PBSC) in patients with treatment-related cytopenia and therefore high risk of bone-marrow failure. Five patients with diffuse bone-marrow infiltration of NET and relevant myelosuppression (≥grade 2) received PBSC before one PRRT cycle with 177Lu-DOTATATE (7.6 ± 0.8 GBq/cycle). Standard stem-cell mobilization with Granulocyte-colony stimulating factor (G-CSF) was applied, and successful PBSC was defined as a collection of >2 × 106/kg CD34+ cells. In case of initial failure, Plerixafor was administered in addition to G-CSF prior to apheresis. PBSC was successfully performed in all patients with no adverse events. Median cumulative activity was 44.8 GBq (range, 21.3–62.4). Three patients had been previously treated with PRRT, two of which needed the addition of Plerixafor for stem-cell mobilization. Only one of five patients required autologous peripheral blood stem-cell transplantation during the median follow up time of 28 months. PBSC collection seems to be feasible in NET with bone-marrow involvement and might be worth considering as a backup strategy prior to PRRT, in order to overcome dose-limiting bone-marrow toxicity.

Published
2021

14. Mechanistic Characterization of Tafasitamab-Mediated Antibody-Dependent Cellular Phagocytosis Alone or in Combination with Lenalidomide

Author

Mougiakakos, Dimitrios, primary, Voelkl, Simon, additional, Bach, Christian, additional, Stoll, Andrej, additional, Bitterer, Katrin, additional, Beier, Fabian, additional, Endell, Jan, additional, Boxhammer, Rainer, additional, Bittenbring, Jörg Thomas, additional, Mackensen, Andreas, additional, and Bruns, Heiko, additional

Published
2019
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15. VEGFR2 and VEGFA polymorphisms are not associated with an inferior prognosis in Caucasian patients with aggressive B‐cell lymphoma.

Author

Kaddu‐Mulindwa, Dominic, Rosolowski, Maciej, Ziepert, Marita, Regitz, Evi, Assmann, Gunter, Bewarder, Moritz, Held, Gerhard, Pfreundschuh, Michael, and Bittenbring, Jörg Thomas

Subjects
DIFFUSE large B-cell lymphomas, SINGLE nucleotide polymorphisms, VASCULAR endothelial growth factor receptors, LYMPHOMAS
Abstract

Purpose: Previous published data showed an impact of single‐nucleotide polymorphisms in the VEGF A and VEGFR2 genes on the survival of patients with various malignancies, among others diffuse large B‐cell lymphoma (DLBCL). Patients and Methods: We investigated the role of four VEGF‐A and two VEGFR‐2 gene polymorphisms on the outcome of 273 patients with diffuse large B‐cell lymphoma who were treated with R‐CHOP within a prospective, randomized trial of the German High‐Grade Non‐Hodgkin Lymphoma Study Group (DSHNHL). The genomic DNA samples were analyzed using commercial DNA Probes (Applied Biosystems, USA) to detect single‐nucleotide polymorphisms in the VEGF A rs699947, rs1570360, rs2010963, rs3025039 and rs1870377, and rs2305948 in the VEGFR2 receptor. Hundred healthy blood donors served as a control. Results: There was no difference between the SNP allele frequencies in lymphoma patients compared to the control group for all investigated SNPs. None of the investigated SNPs was significantly associated with EFS or OS. After adjusting for the International Prognostic Index risk factors in a multivariate analysis, these results could be confirmed. Conclusion: Single‐nucleotide polymorphisms of the VEGF and VEGFR2 were not associated with a worse outcome in Caucasian patients with DLBCL. [ABSTRACT FROM AUTHOR]

Published
2021
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16. Gene Set Enrichment Analysis Suggests That Increased Rituximab-Mediated NK Cell Cytotoxicity after Vitamin D Substitution Is Driven By Upregulation of Interferon Alpha (IFN-a) Isoforms

Author

Christofyllakis, Konstantinos, primary, Neumann, Frank, additional, Stilgenbauer, Stephan, additional, Kaddu-Mulindwa, Dominic, additional, Regitz, Evi, additional, Bewarder, Moritz, additional, Keller, Andreas, additional, and Bittenbring, Jörg Thomas, additional

Published
2018
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17. Donor Lymphocyte Infusions for the Treatment of Relapsed Non-Hodgkin Lymphoma Following Allogeneic Stem Cell Transplantation: A LWP-EBMT Study

Author

Robinson, Stephen, primary, Boumendil, Ariane, additional, Finel, Hervé, additional, Khvedelidze, Irma, additional, Kanfer, Edward, additional, Peggs, Karl, additional, Furst, Sabine, additional, Ram, Ron, additional, Marijt, Waf, additional, Vandenberghe, Elisabeth, additional, Afanasiev, Boris, additional, Wulf, Gerald, additional, Chalandon, Yves, additional, Maertens, Johan, additional, Tsoulkani, Anna, additional, Schaap, Michel, additional, Beelen, Dietrich W., additional, Gurman, Gunhan, additional, Finke, Jürgen, additional, Wittnebel, Sebastian, additional, Di Bartolomeo, Paolo, additional, Tischer, Johanna, additional, Corradini, Paolo, additional, Caballero, Dolores, additional, Marzolini, Maria A V, additional, Burney, Claire, additional, La Nasa, Giorgio, additional, Potter, Victoria, additional, Bittenbring, Jörg Thomas, additional, Fegueux, Nathalie, additional, Kroeger, Nicolaus, additional, Schmitz, Norbert, additional, Dreger, Peter, additional, and Montoto, Silvia, additional

Published
2018
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18. Differential effects of endurance, interval, and resistance training on telomerase activity and telomere length in a randomized, controlled study

Author

Werner, Christian M, primary, Hecksteden, Anne, additional, Morsch, Arne, additional, Zundler, Joachim, additional, Wegmann, Melissa, additional, Kratzsch, Jürgen, additional, Thiery, Joachim, additional, Hohl, Mathias, additional, Bittenbring, Jörg Thomas, additional, Neumann, Frank, additional, Böhm, Michael, additional, Meyer, Tim, additional, and Laufs, Ulrich, additional

Published
2018
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19. Vitamin D deficiency in head and neck cancer patients – prevalence, prognostic value and impact on immune function

Author

Bochen, Florian, primary, Balensiefer, Benedikt, additional, Körner, Sandrina, additional, Bittenbring, Jörg Thomas, additional, Neumann, Frank, additional, Koch, Armand, additional, Bumm, Klaus, additional, Marx, Anke, additional, Wemmert, Silke, additional, Papaspyrou, Georgios, additional, Zuschlag, David, additional, Kühn, Jan Philipp, additional, Al Kadah, Basel, additional, Schick, Bernhard, additional, and Linxweiler, Maximilian, additional

Published
2018
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21. Einfluss des Vitamin D3 Serumspiegels auf die lymphogene Metastasierung, sowie die zytotoxische Aktivität von Natürlichen Killerzellen in Patienten mit Kopf-Hals-Tumoren

Author

Bochen, Florian, Bittenbring, Jörg Thomas, Neumann, Frank, Schick, Bernhard, and Linxweiler, Maximilian

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Einleitung: Aktuelle Studien zeigen unzureichende Vitamin D3 Serumspiegel von Patienten mit Plattenepithelkarzinomen des Kopf-Hals-Bereichs (HNSCC) und weisen auf einen Zusammenhang zu einer schlechteren Prognose hin. In dieser Studie haben wir sowohl die Prävalenz eines Vitamin D3 Mangels als auch die zytotoxische Aktivität der Natürlichen Killerzellen (ADCC) von HNSCC-Patienten vor und nach Vitamin D3 Substitution untersucht. Methoden: Es wurden Blutproben von 107 HNSCC-Patienten und 98 gesunden Probanden gesammelt und ihr 25-OH-Vitamin D Serumspiegel bestimmt. Für eine Auswahl beider Gruppen wurde zusätzlich die ADCC gegenüber FaDu-Zellen ermittelt. Dies erfolgte mit Hilfe eines Lactatdehydrogenase-Tests, jeweils mit oder ohne Zugabe von Cetuximab. Dieselben Probanden erhielten für 12 Wochen 2.000 IE Vitamin D3 pro Tag. Anschließend wurden Blutproben entnommen, um den Vitamin D3 Serumspiegel und die ADCC zu bestimmen. Ergebnisse: Die untersuchten HNSCC-Patienten wiesen im Vergleich zu den gesunden Probanden einen hoch signifikanten Vitamin D3 Mangel auf (p, GMS Current Posters in Otorhinolaryngology - Head and Neck Surgery; 12:Doc186

Published
2016
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22. Differential effects of endurance, interval, and resistance training on telomerase activity and telomere length in a randomized, controlled study.

Author

Werner, Christian M, Hecksteden, Anne, Morsch, Arne, Zundler, Joachim, Wegmann, Melissa, Kratzsch, Jürgen, Thiery, Joachim, Hohl, Mathias, Bittenbring, Jörg Thomas, Neumann, Frank, Böhm, Michael, Meyer, Tim, and Laufs, Ulrich

Abstract

Aims It is unknown whether different training modalities exert differential cellular effects. Telomeres and telomere-associated proteins play a major role in cellular aging with implications for global health. This prospective training study examines the effects of endurance training, interval training (IT), and resistance training (RT) on telomerase activity and telomere length (TL). Methods and results One hundred and twenty-four healthy previously inactive individuals completed the 6 months study. Participants were randomized to three different interventions or the control condition (no change in lifestyle): aerobic endurance training (AET, continuous running), high-intensive IT (4 × 4 method), or RT (circle training on 8 devices), each intervention consisting of three 45 min training sessions per week. Maximum oxygen uptake (VO2max) was increased by all three training modalities. Telomerase activity in blood mononuclear cells was up-regulated by two- to three-fold in both endurance exercise groups (AET, IT), but not with RT. In parallel, lymphocyte, granulocyte, and leucocyte TL increased in the endurance-trained groups but not in the RT group. Magnet-activated cell sorting with telomerase repeat-ampliflication protocol (MACS-TRAP) assays revealed that a single bout of endurance training—but not RT—acutely increased telomerase activity in CD14+ and in CD34+ leucocytes. Conclusion This randomized controlled trial shows that endurance training, IT, and RT protocols induce specific cellular pathways in circulating leucocytes. Endurance training and IT, but not RT, increased telomerase activity and TL which are important for cellular senescence, regenerative capacity, and thus, healthy aging. View large Download slide View large Download slide [ABSTRACT FROM AUTHOR]

Published
2019
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23. Remission Status at Transplantation and Treatment History Determine the Survival Chances of Patients after Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia Who Had Received Pre-Treatment with Idelalisib: A Report from the EBMT Chronic Malignancies Working Party

Author

Schetelig, Johannes, Chevallier, Patrice, Van Gelder, Michel, Hoek, Jennifer, Hermine, Olivier, Chakraverty, Ronjon, Browne, Paul, Milpied, Noel, Malagola, Michele, Socie, Gerard, Delgado, Julio, Deconinck, Eric, Damaj, Gandhi, Cordonnier, Catherine, Beelen, Dietrich W, Nguyen, Stephanie, Nikolousis, Emmanouil, Brecht, Arne, Mayer, Jiri, Hunault, Mathilde, Bittenbring, Jörg Thomas, Thieblemont, Catherine, Leprêtre, Stéphane, de Wreede, Liesbeth C, Dreger, Peter, and Kröger, Nicolaus

Published
2017
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24. In the Era of Chemoimmunotherapy, Relapse Post Autologous Stem Cell Transplantation for Follicular Lymphoma Is Associated with Prolonged Overall Survival. an Analysis By the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

Author

Robinson, Stephen, Finel, Hervé, Boumendil, Ariane, Tilly, Herve, Salles, Gilles, Corradini, Paolo, Cairoli, Roberto, Pytlik, Robert, Schouten, Harry C., Lewerin, Catharina, Thieblemont, Catherine, Metzner, Bernd, Rambaldi, Alessandro, Ringhoffer, Mark, Lown, Robert, Rossi, Giuseppe, Bittenbring, Jörg Thomas, Bloor, Adrian, Illés, Árpád, Feugier, Pierre, Turlure, Pascal, Mufti, Ghulam, Heinicke, Thomas, Peggs, Karl, Poire, Xavier, Dreger, Peter, and Montoto, Silvia

Published
2017
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25. Management and Outcome of Patients with Diffuse Large B-Cell Lymphoma Relapsed after Autologous Hemopoietic Stem Cell Transplantation (auto-HSCT): A Retrospective Analysis of the Lymphoma Working Party (LWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Author

Gonzalez-Barca, Eva, Boumendil, Ariane, Blaise, Didier, Trněný, Marek, Masszi, Tamas, Finel, Hervé, Michieli, Mariagrazia, Bittenbring, Jörg Thomas, Gritti, Giuseppe, Snowden, John A., Bishton, Mark, Bruno, Benedetto, González de Villambrosia, Sonia, Janikova, Andrea, Leleu, Xavier, Anagnostopoulos, Achilles, Poire, Xavier, Crysandt, Martina, Nur Özkurt, Zübeyde, Vandenberghe, Elisabeth, Itälä-Remes, Maija, Cahn, Jean-Yves, Jantunen, Esa, Schroyens, Wilfried, Maertens, Johan, Esquirol, Albert, Dreger, Peter, Montoto, Silvia, and Sureda, Anna

Published
2017
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26. Elektrophysiologische Charakterisierung und pharmakologische Blockade von Listeriolysin O-induzierten Membranporen

Author

Bittenbring, Jörg Thomas and Justus Liebig University Giessen

Subjects
Eosin Y, block, ddc:610, LLO, Lanthanoide, lanthanides, Porenblockade
Abstract

Listeriolysin O (LLO), ein porenbildendes Toxin aus der Gruppe der Cholesterolabhängigen Zytolysine (CDTX), ist ein essentieller Pathogenitätsfaktor des humanpathogenen Bakteriums Listeria monocytogenes.In dieser Arbeit konnte elektrophysiologisch direkt nachgewiesen werden, dass Dithiotreitol (DTT) und saure (5,9) pH-Werte die porenbildende Aktivität von LLO um das 3-5fache steigern. Offene LLO-Poren schliessen in der Whole-Cell Messkonfiguration gleich häufig schnell oder langsam. Nominell Ca2+-freie Intrazellulärlösung führte zu einer signifikanten Abnahme langsamer Porenschlüsse, zugunsten schneller Porenschlüsse. In den Outside-Out Patches sind beide Formen des Porenschlusses hochsignifikant seltener, wobei langsame Porenschlüsse signifikant seltener sind als statistisch im Vergleich zu den schnellen Porenschlüssen zu erwarten ist. Dies passt gut zu der Hypothese, dass es sich bei den langsamenPorenschlüssen um Endozytose-Prozesse handelt. In Inside-Out Patches konntedirekt gezeigt werden, dass LLO in der zytoplasmatischen Seite der ZellmembranPoren induzieren kann, was bei der interzellulären Ausbreitung von L.monocytogenes von entscheidender Bedeutung ist. Im Rahmen eines Screeningsauf Poren-blockierende Substanzen konnte gezeigt werden, dass die LLO-Porendurch trivalente Ionen, wie Lanthanoide und Aluminium vollständig blockiertwurden. Es handelte sich hierbei um einen vom Ionenradius abhängigen,reversiblen und membranpotentialabhängigen Block. Die zweiwertigen Metall-Ionen, wie Cd2+, Ni2+, Ru2+ und Zn2+ blockierten die LLO-induzierten Porenströme nur teilweise. Eosin Y war der einzige nicht-metallische Blocker der LLO-Poren. LLO-induzierte Ca2+-Oszillationen wurden durch Gd3+ vollständig blockiert. Im Gegensatz dazu konnten Inhibitoren der intrazellulären Ca2+-Freisetzung oder von Ca2+-Kanälen die Ca2+-Oszillationen nicht verändern. Dies zeigt, dass der Anstieg der intrazellulären Ca2+-Konzentration bei den LLO-induzierten Ca2+-Oszillationenallein durch die LLO-Poren bedingt ist. Die Blockade der plasmamembranständigen Ca2+-ATPasen (PMCA) durch Gd3+ führt zur HemmungCa2+-Sequestration bei LLO -induzierten Ca2+-Oszillationen. Das unterstreicht die entscheidende Rolle der PMCA bei den LLO-induzierten Ca2+-Oszillationen., Listeriolysin O is a pore-forming toxin belonging to the familiy of cholesteroldependent cytolysins and is the major pathogenicity factor of L. monocytogenes. By electrophysiological measurement studies, it could be directly shown that dithiotreitol (DTT) and acidic (5.9) pH raise LLOs pore-forming activity 3 to 5 fold. In whole-cell measurements LLO-pores close equally often in a quick or slow way. Ca2+-free intracellular medium leads to a significant decrease in slow closings in favour of fast closings. In outside-out patches both types of pore closings were significantly decreased compared to whole-cell measurements. Compared to the quick closings the slow closings were furthermore significantly reduced. This observation favours our hypothesis that slow closings are caused by endocytosis. As clearly shown in the above study, pore formation in inside-out patches proves that LLO can form pores in the cytoplasmatic leaflet of the cell membrane which underlines its importance in cell-to-cell spreading. On screening several substances for pore blocking abilities, we found several of them that could block the LLO-pores. The trivalent ions like lanthanoids and aluminium blocked the LLO-pores completely. This block induced by lanthanoid was fully reversible and voltage dependent. The IC50 of lanthanoids was dependent on its ionic radius. Divalent ions like cadmium, nickel, zinc and ruthenium only partially blocked the current evoked by LLO-pores. Eosin Y could be identified as a non-metal pore blocking agent.LLO induced Ca2+-oscillations were completely blocked by Gd3+ whereas blocking the intracellular Ca2+-release or Ca2+-channels did not lead to any changes. This clearly shows that the Ca2+-influx exclusively goes through the LLO-pores. Gd3+ also blocks plasma membrane Ca2+-ATPases thereby inhibiting Ca2+- sequestration in LLO-induced Ca2+-oscillations. This implies the importance of PMCAs in LLO-induced Ca2+-oscillations.

Published
2005
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27. Vitamin D Deficiency Impairs Rituximab-Mediated Cellular Cytotoxicity and Outcome of Patients With Diffuse Large B-Cell Lymphoma Treated With but Not Without Rituximab

Author

Bittenbring, Jörg Thomas, primary, Neumann, Frank, additional, Altmann, Bettina, additional, Achenbach, Marina, additional, Reichrath, Jörg, additional, Ziepert, Marita, additional, Geisel, Jürgen, additional, Regitz, Evi, additional, Held, Gerhard, additional, and Pfreundschuh, Michael, additional

Published
2014
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29. Outcomes of Mismatched Related Allogeneic Stem Cell Transplantation for Chronic Lymphocytic Leukemia: A Retrospective Study on Behalf of the Chronic Malignancies Working Party of the EBMT

Author

van Gorkom, Gwendolyn, van Gelder, Michel, Ziagkos, Dimitris, Blok, Henric-Jan, van Lint, Maria Teresa, Koc, Yener, Ciceri, Fabio, Beelen, Dietrich W., Chevallier, Patrice, Selleslag, Dominik, Blaise, Didier, Foà, Roberto, Corradini, Paolo, Castagna, Luca, Moreno, Carol, Solano, Carlos, Müller, Lutz P., Tischer, Johanna, Hilgendorf, Inken, Hallek, Michael, Bittenbring, Joerg Thomas, Theobald, Matthias, Schetelig, Johannes, and Kröger, Nicolaus

Published
2016
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32. Elektrophysiologische Charakterisierung und pharmakologische Blockade von Listeriolysin O-induzierten Membranporen

Author

Rudolf-Buchheim-Institut für Pharmakologie, Bittenbring, Jörg Thomas, Rudolf-Buchheim-Institut für Pharmakologie, and Bittenbring, Jörg Thomas

Abstract

Listeriolysin O (LLO), ein porenbildendes Toxin aus der Gruppe der Cholesterolabhängigen Zytolysine (CDTX), ist ein essentieller Pathogenitätsfaktor des humanpathogenen Bakteriums Listeria monocytogenes. In dieser Arbeit konnte elektrophysiologisch direkt nachgewiesen werden, dass Dithiotreitol (DTT) und saure (5,9) pH-Werte die porenbildende Aktivität von LLO um das 3-5fache steigern. Offene LLO-Poren schliessen in der Whole-Cell Messkonfiguration gleich häufig schnell oder langsam. Nominell Ca2+-freie Intrazellulärlösung führte zu einer signifikanten Abnahme langsamer Porenschlüsse, zugunsten schneller Porenschlüsse. In den Outside-Out Patches sind beide Formen des Porenschlusses hochsignifikant seltener, wobei langsame Porenschlüsse signifikant seltener sind als statistisch im Vergleich zu den schnellen Porenschlüssen zu erwarten ist. Dies passt gut zu der Hypothese, dass es sich bei den langsamen Porenschlüssen um Endozytose-Prozesse handelt. In Inside-Out Patches konnte direkt gezeigt werden, dass LLO in der zytoplasmatischen Seite der Zellmembran Poren induzieren kann, was bei der interzellulären Ausbreitung von L. monocytogenes von entscheidender Bedeutung ist. Im Rahmen eines Screenings auf Poren-blockierende Substanzen konnte gezeigt werden, dass die LLO-Poren durch trivalente Ionen, wie Lanthanoide und Aluminium vollständig blockiert wurden. Es handelte sich hierbei um einen vom Ionenradius abhängigen, reversiblen und membranpotentialabhängigen Block. Die zweiwertigen Metall- Ionen, wie Cd2+, Ni2+, Ru2+ und Zn2+ blockierten die LLO-induzierten Porenströme nur teilweise. Eosin Y war der einzige nicht-metallische Blocker der LLO-Poren. LLO-induzierte Ca2+-Oszillationen wurden durch Gd3+ vollständig blockiert. Im Gegensatz dazu konnten Inhibitoren der intrazellulären Ca2+-Freisetzung oder von Ca2+-Kanälen die Ca2+-Oszillationen nicht verändern. Dies zeigt, dass der Anstieg der intrazellulären Ca2+-Konzentration bei den LLO-induzierten Ca2+-Oszillationen a, Listeriolysin O is a pore-forming toxin belonging to the familiy of cholesteroldependent cytolysins and is the major pathogenicity factor of L. monocytogenes. By electrophysiological measurement studies, it could be directly shown that dithiotreitol (DTT) and acidic (5.9) pH raise LLOs pore-forming activity 3 to 5 fold. In whole-cell measurements LLO-pores close equally often in a quick or slow way. Ca2+-free intracellular medium leads to a significant decrease in slow closings in favour of fast closings. In outside-out patches both types of pore closings were significantly decreased compared to whole-cell measurements. Compared to the quick closings the slow closings were furthermore significantly reduced. This observation favours our hypothesis that slow closings are caused by endocytosis. As clearly shown in the above study, pore formation in inside-out patches proves that LLO can form pores in the cytoplasmatic leaflet of the cell membrane which underlines its importance in cell-to-cell spreading. On screening several substances for pore blocking abilities, we found several of them that could block the LLO-pores. The trivalent ions like lanthanoids and aluminium blocked the LLO-pores completely. This block induced by lanthanoid was fully reversible and voltage dependent. The IC50 of lanthanoids was dependent on its ionic radius. Divalent ions like cadmium, nickel, zinc and ruthenium only partially blocked the current evoked by LLO-pores. Eosin Y could be identified as a non-metal pore blocking agent. LLO induced Ca2+-oscillations were completely blocked by Gd3+ whereas blocking the intracellular Ca2+-release or Ca2+-channels did not lead to any changes. This clearly shows that the Ca2+-influx exclusively goes through the LLO-pores. Gd3+ also blocks plasma membrane Ca2+-ATPases thereby inhibiting Ca2+- sequestration in LLO-induced Ca2+-oscillations. This implies the importance of PMCAs in LLO-induced Ca2+-oscillations.

Published
2005

33. Sequential Intensified Conditioning Regimen Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with High-Risk AML in Complete Remission: A Survey from the ALWP of the EBMT

Author

Malard, Florent, Labopin, Myriam, Stuhler, Gernot, Tischer, Johanna, Bittenbring, Joerg Thomas, Ganser, Arnold, Kroeger, Nicolaus, Bunjes, Donald, Schmid, Christoph, Mayer, Jiri, Michallet, Mauricette, Hallek, Michael, Savani, Bipin N., Mohty, Mohamad, and Nagler, Arnon

Published
2015
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38. Prophylactic Peripheral Blood Stem Cell Collection in Patients with Extensive Bone-Marrow Infiltration of Neuroendocrine Tumours Prior to Peptide Receptor Radionuclide Therapy with 177 Lu-DOTATATE.

Author

Sabet, Amir, Mader, Nicolai, Bittenbring, Jörg Thomas, Khreish, Fadi, Grünwald, Frank, Biersack, Hans Jürgen, and Ezziddin, Samer

Subjects
PEPTIDE receptors, NEUROENDOCRINE tumors, STEM cells, GRANULOCYTE-colony stimulating factor, BLOOD cells
Abstract

Peptide receptor radionuclide therapy (PRRT) of metastatic neuroendocrine tumors (NET) can be successfully repeated but may eventually be dose-limited. Since 177Lu-DOTATATE dose limitation may come from hematological rather than renal function, hematological peripheral blood stem cell backup might be desirable. Here, we report our initial experience of peripheral blood stem-cell collection (PBSC) in patients with treatment-related cytopenia and therefore high risk of bone-marrow failure. Five patients with diffuse bone-marrow infiltration of NET and relevant myelosuppression (≥grade 2) received PBSC before one PRRT cycle with 177Lu-DOTATATE (7.6 ± 0.8 GBq/cycle). Standard stem-cell mobilization with Granulocyte-colony stimulating factor (G-CSF) was applied, and successful PBSC was defined as a collection of >2 × 106/kg CD34+ cells. In case of initial failure, Plerixafor was administered in addition to G-CSF prior to apheresis. PBSC was successfully performed in all patients with no adverse events. Median cumulative activity was 44.8 GBq (range, 21.3–62.4). Three patients had been previously treated with PRRT, two of which needed the addition of Plerixafor for stem-cell mobilization. Only one of five patients required autologous peripheral blood stem-cell transplantation during the median follow up time of 28 months. PBSC collection seems to be feasible in NET with bone-marrow involvement and might be worth considering as a backup strategy prior to PRRT, in order to overcome dose-limiting bone-marrow toxicity. [ABSTRACT FROM AUTHOR]

Published
2021
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42. Blockade of the CD47/SIRPα checkpoint axis potentiates the macrophage-mediated antitumor efficacy of tafasitamab.

Author

Biedermann A, Patra-Kneuer M, Mougiakakos D, Büttner-Herold M, Mangelberger-Eberl D, Berges J, Kellner C, Altmeyer S, Bittenbring JT, Augsberger C, Ilieva-Babinsky K, Haskamp S, Beier F, Lischer C, Vera J, Lührmann A, Bertz S, Völkl S, Jacobs B, Steidl S, Mackensen A, and Bruns H

Subjects
Humans, Animals, Mice, Cell Line, Tumor, Phagocytosis drug effects, Tumor Microenvironment drug effects, Antibodies, Monoclonal, Humanized pharmacology, Antibodies, Monoclonal, Humanized therapeutic use, CD47 Antigen metabolism, CD47 Antigen antagonists & inhibitors, Receptors, Immunologic metabolism, Receptors, Immunologic antagonists & inhibitors, Antigens, Differentiation metabolism, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse metabolism, Lymphoma, Large B-Cell, Diffuse pathology, Macrophages metabolism, Macrophages drug effects, Macrophages immunology, Xenograft Model Antitumor Assays
Abstract

Macrophages are one of the key mediators of the therapeutic effects exerted by monoclonal antibodies, such as the anti-CD19 antibody tafasitamab, approved in combination with lenalidomide for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL). However, antibody-dependent cellular phagocytosis (ADCP) in the tumor microenvironment can be counteracted by increased expression of the inhibitory receptor SIRPα on macrophages and its ligand, the immune checkpoint molecule CD47, on tumor cells. The aim of this study was to investigate the impact of the CD47-SIRPα axis on tafasitamab- mediated phagocytosis and explore the potential of anti-CD47 blockade to enhance its antitumor activity. Elevated expression of both SIRPα and CD47 was observed in DLBCL patient-derived lymph node biopsies compared to healthy control lymph nodes. CRISPR-mediated CD47 overexpression affected tafasitamab-mediated ADCP in vitro and increased expression of SIRPα on macrophages correlated with decreased ADCP activity of tafasitamab against DLBCL cell lines. A combination of tafasitamab and an anti-CD47 blocking antibody enhanced ADCP activity of in vitro-generated macrophages. Importantly, tafasitamab-mediated phagocytosis was elevated in combination with CD47 blockade using primary DLBCL cells and patient-derived lymphoma-associated macrophages in an autologous setting. Furthermore, lymphoma cells with low CD19 expression were efficiently eliminated by the combination treatment. Finally, combined treatment of tafasitamab and an anti-CD47 antibody resulted in enhanced tumor volume reduction and survival benefit in lymphoma xenograft mouse models. These findings provide evidence that CD47 blockade can enhance the phagocytic potential of tumor-targeting immunotherapies such as tafasitamab and suggest that there is value in exploring the combination in the clinic.

Published
2024
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