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40 results on '"Schneidawind, Corina"'

3. Treatment response of advanced HNSCC towards immune checkpoint inhibition is associated with an activated effector memory T cell phenotype

Author

Schumacher, Max, primary, Beer, Sina, additional, Moraes Ribeiro, Emmanuelle, additional, Korkmaz, Fulya, additional, Keppeler, Hildegard, additional, Fitzel, Rahel, additional, Erkner, Estelle, additional, Radszuweit, Pia, additional, Lengerke, Claudia, additional, Schneidawind, Corina, additional, Hoefert, Sebastian, additional, Mauz, Paul Stefan, additional, and Schneidawind, Dominik, additional

Published
2024
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4. B‐cell maturation antigen‐directed bispecific antibodies in plasmablastic lymphoma.

Author

Hofer, Kevin D., Wolfensberger, Nathan, Bachofner, Adrian, Schneidawind, Corina, Stühler, Claudia, Bühler, Marco M., Abela, Irene A., Müller, Nicolas J., Zenz, Thorsten, Manz, Markus G., Rösler, Wiebke, Khanna, Nina, and Schneidawind, Dominik

Subjects
T helper cells, NUCLEIC acid hybridization, BISPECIFIC antibodies, JAK-STAT pathway, DIAGNOSIS of HIV infections
Abstract

Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of large B‐cell lymphoma that primarily affects individuals with immunodeficiency, particularly those who are HIV positive. PBL commonly presents in males at an advanced stage and often affects extranodal regions such as the oral cavity and gastrointestinal tract. The prognosis for PBL is poor, with limited treatment options and low overall survival rates. This article discusses the potential use of bispecific antibodies, specifically teclistamab, in the treatment of refractory PBL in an HIV-positive patient. The case study highlights the efficacy of teclistamab and the importance of donor selection for allogeneic stem cell transplantation in EBV-positive lymphomas. However, further research is needed to establish standardized treatment guidelines for PBL. [Extracted from the article]

Published
2024
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5. PD-1 checkpoint inhibition enhances the antilymphoma activity of CD19-CAR-iNKT cells that retain their ability to prevent alloreactivity

Author

Moraes Ribeiro, Emmanuelle, primary, Secker, Kathy-Ann, additional, Nitulescu, Ana-Maria, additional, Schairer, Rebekka, additional, Keppeler, Hildegard, additional, Wesle, Anton, additional, Schmid, Hannes, additional, Schmitt, Anita, additional, Neuber, Brigitte, additional, Chmiest, Daniela, additional, Podavini, Silvia, additional, Märklin, Melanie, additional, Klimovich, Boris, additional, Schmitt, Michael, additional, Korkmaz, Fulya, additional, Lengerke, Claudia, additional, Schneidawind, Corina, additional, and Schneidawind, Dominik, additional

Published
2024
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6. The RORɣ/SREBP2 pathway is a master regulator of cholesterol metabolism and serves as potential therapeutic target in t(4;11) leukemia

Author

Erkner, Estelle, primary, Hentrich, Thomas, additional, Schairer, Rebekka, additional, Fitzel, Rahel, additional, Secker-Grob, Kathy-Ann, additional, Jeong, Johan, additional, Keppeler, Hildegard, additional, Korkmaz, Fulya, additional, Schulze-Hentrich, Julia M., additional, Lengerke, Claudia, additional, Schneidawind, Dominik, additional, and Schneidawind, Corina, additional

Published
2023
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17. The Rorɣ/SREBP2 Pathway Is a Master Regulator of Cholesterol Metabolism and Serves As Potential Therapeutic Target in T(4;11) Leukemia

Author

Erkner, Estelle, primary, Hentrich, Thomas, additional, Fitzel, Rahel, additional, Keppeler, Hildegard, additional, Korkmaz, Fulya, additional, Jeong, Johan, additional, Schulze-Hentrich, Julia, additional, Lengerke, Claudia, additional, Schneidawind, Dominik, additional, and Schneidawind, Corina, additional

Published
2022
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18. Low Graft Invariant Natural Killer T-Cell Dose Is a Risk Factor for Cytomegalovirus Reactivation After Allogeneic Hematopoietic Cell Transplantation

Author

Schneidawind, Dominik, primary, Duerr-Stoerzer, Silke, additional, Liewer, Sonja, additional, Renner, Susanne, additional, Sánchez Navarro, Beatriz, additional, Atar, Daniel, additional, Keppeler, Hildegard, additional, Beck, Robert, additional, Hamprecht, Klaus, additional, Kanz, Lothar, additional, Lengerke, Claudia, additional, and Schneidawind, Corina, additional

Published
2022
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20. Human invariant natural killer T cells promote tolerance by preferential apoptosis induction of conventional dendritic cells

Author

Schmid, Hannes, primary, Ribeiro, Emmanuelle M., additional, Secker, Kathy-Ann, additional, Duerr-Stoerzer, Silke, additional, Keppeler, Hildegard, additional, Dong, Ruoyun, additional, Munz, Timo, additional, Schulze-Osthoff, Klaus, additional, Hailfinger, Stephan, additional, Schneidawind, Corina, additional, and Schneidawind, Dominik, additional

Published
2021
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21. Additional file 1 of Inhibition of effector B cells by ibrutinib in systemic sclerosis

Author

Einhaus, Jakob, Ann-Christin Pecher, Asteriti, Elisa, Schmid, Hannes, Kathy-Ann Secker, Duerr-Stoerzer, Silke, Keppeler, Hildegard, Klein, Reinhild, Schneidawind, Corina, Joerg Henes, and Schneidawind, Dominik

Abstract

Supplemental Figure 1. Cytokine production by B cells of healthy volunteers with ibrutinib treatment (n = 4). B cells of healthy volunteers were stimulated with CpG for 24 h and treated with DMSO (Control) or ibrutinib (10 μM). With a Legendplex assay, cytokine levels of IL-6, TNF-⍺, IFN-γ and IL-10 were determined in the culture supernatant. Bars represent mean. Error bars indicate SEM. * p

Published
2020
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23. MAT2A as Key Regulator and Therapeutic Target in MLLr Leukemogenesis

Author

Secker, Kathy-Ann, primary, Bloechl, Bianca, additional, Keppeler, Hildegard, additional, Duerr-Stoerzer, Silke, additional, Schmid, Hannes, additional, Schneidawind, Dominik, additional, Jeong, Johan, additional, Hentrich, Thomas, additional, Schulze-Hentrich, Julia M., additional, and Schneidawind, Corina, additional

Published
2020
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24. Invariant NKT Cells From Donor Lymphocyte Infusions (DLI-iNKTs) Promote ex vivo Lysis of Leukemic Blasts in a CD1d-Dependent Manner

Author

Jahnke, Simona, Schmid, Hannes, Secker, Kathy-Ann, Einhaus, Jakob, Duerr-Stoerzer, Silke, Keppeler, Hildegard, Schober-Melms, Irmtraud, Baur, Rebecca, Schumm, Michael, Handgretinger, Rupert, Bethge, Wolfgang, Kanz, Lothar, Schneidawind, Corina, and Schneidawind, Dominik

Subjects
lcsh:Immunologic diseases. Allergy, Immunology, GVHD, Graft vs Host Disease, Graft vs Leukemia Effect, Immunotherapy, Adoptive, Jurkat Cells, Cell Line, Tumor, Humans, Transplantation, Homologous, Lymphocytes, hematopoietic cell transplantation, Cells, Cultured, iNKT cells, Original Research, Bone Marrow Transplantation, Leukemia, Hematopoietic Stem Cell Transplantation, Progression-Free Survival, Tissue Donors, GVL, Hematologic Neoplasms, Lymphocyte Transfusion, Natural Killer T-Cells, Antigens, CD1d, K562 Cells, DLI, lcsh:RC581-607, adoptive immunotherapy
Abstract

Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative treatment option for hematologic malignancies but relapse remains the most common cause of death. Infusion of donor lymphocytes (DLIs) can induce remission and prolong survival by exerting graft-vs.-leukemia (GVL) effects. However, sufficient tumor control cannot be established in all patients and occurrence of graft-vs.-host disease (GVHD) prevents further dose escalation. Previous data indicate that invariant natural killer T (iNKT) cells promote anti-tumor immunity without exacerbating GVHD. In the present study we investigated lysis of leukemic blasts through iNKT cells from donor-derived lymphocytes for leukemia control and found that iNKT cells constitute about 0.12% of cryopreserved donor T cells. Therefore, we established a 2-week cell culture protocol allowing for a robust expansion of iNKT cells from cryopreserved DLIs (DLI-iNKTs) that can be used for further preclinical and clinical applications. Such DLI-iNKTs efficiently lysed leukemia cell lines and primary patient AML blasts ex vivo in a dose- and CD1d-dependent manner. Furthermore, expression of CD1d on target cells was required to release proinflammatory cytokines and proapoptotic effector molecules. Our results suggest that iNKT cells from donor-derived lymphocytes are involved in anti-tumor immunity after allo-HCT and therefore may reduce the risk of relapse and improve progression-free and overall survival.

Published
2019

26. Invariant Natural Killer T Cells from Donor Lymphocyte Infusions (DLI-iNKTs) Contribute to Anti-Tumor Immunity after Allogeneic Hematopoietic Cell Transplantation

Author

Jahnke, Simona, primary, Schmid, Hannes, additional, Secker, Kathy-Ann, additional, Duerr-Stoerzer, Silke, additional, Keppeler, Hildegard, additional, Baur, Rebecca, additional, Schumm, Michael, additional, Handgretinger, Rupert, additional, Bethge, Wolfgang, additional, Kanz, Lothar, additional, Schneidawind, Corina, additional, and Schneidawind, Dominik, additional

Published
2018
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28. Inhibition of DOT1L and PRMT5 Promotes Anti-Tumor Activity in a Human MLL Leukemia Model Induced By CRISPR/Cas9

Author

Secker, Kathy-Ann, primary, Keppeler, Hildegard, additional, Duerr-Stoerzer, Silke, additional, Schmid, Hannes, additional, Schneidawind, Dominik, additional, Hentrich, Thomas, additional, Schulze-Hentrich, Julia, additional, Mankel, Barbara, additional, Fend, Falko, additional, Kanz, Lothar, additional, and Schneidawind, Corina, additional

Published
2018
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30. MLL leukemia induction by t(9;11) chromosomal translocation in human hematopoietic stem cells using genome editing

Author

Schneidawind, Corina, primary, Jeong, Johan, additional, Schneidawind, Dominik, additional, Kim, In-Suk, additional, Duque-Afonso, Jesús, additional, Wong, Stephen Hon Kit, additional, Iwasaki, Masayuki, additional, Breese, Erin H., additional, Zehnder, James L., additional, Porteus, Matthew, additional, and Cleary, Michael L., additional

Published
2018
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34. Inhibition of DOT1L and PRMT5 promote synergistic anti-tumor activity in a human MLLleukemia model induced by CRISPR/Cas9

Author

Secker, Kathy-Ann, Keppeler, Hildegard, Duerr-Stoerzer, Silke, Schmid, Hannes, Schneidawind, Dominik, Hentrich, Thomas, Schulze-Hentrich, Julia M., Mankel, Barbara, Fend, Falko, and Schneidawind, Corina

Abstract

MLLrearrangements play a crucial role in leukemogenesis and comprise a poor prognosis. Therefore, new treatment strategies are urgently needed. We used the CRISPR/Cas9 system to generate an innovative leukemia model based on 100% pure MLL-AF4or -AF9rearranged cells derived from umbilical cord blood with indefinite growth in cell culture systems. Our model shared phenotypical, morphological and molecular features of patient cells faithfully mimicking the nature of the disease. Thus, it serves as a fundamental basis for pharmacological studies: inhibition of histone methyltransferase disruptor of telomeric silencing 1-like (DOT1L) is one specific therapeutic approach currently tested in clinical trials. However, success was limited by restricted response warranting further investigation of drug combinations. Recently, it has been shown that the inhibition of protein arginine methyltransferase 5 (PRMT5) exhibits anti-tumoral activity against human cell lines and in MLLmouse models. Here, we used DOT1L and PRMT5 inhibitors in our human MLL-rearranged model demonstrating dose-dependent reduced proliferation, impairment of cell cycle, increasing differentiation, apoptosis, downregulation of target genes and sensitization to chemotherapy. Strikingly, the combination of both compounds led to synergistic anti-tumoral effects. Our study provides a strong rationale for novel targeted combination therapies to improve the outcome of MLL-rearranged leukemias.

Published
2019
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38. Inhibition of DOT1L and PRMT5 Promotes Anti-Tumor Activity in a Human MLLLeukemia Model Induced By CRISPR/Cas9

Author

Secker, Kathy-Ann, Keppeler, Hildegard, Duerr-Stoerzer, Silke, Schmid, Hannes, Schneidawind, Dominik, Hentrich, Thomas, Schulze-Hentrich, Julia, Mankel, Barbara, Fend, Falko, Kanz, Lothar, and Schneidawind, Corina

Abstract

MLLrearrangements play a crucial role in leukemogenesis. They are associated with a poor prognosis and new treatment strategies are urgently needed. Here, we used the CRISPR/Cas9 system to generate an innovative leukemia model based on 100% pure MLL-AF4/-AF9rearranged cells derived from umbilical cord blood with indefinite growth in cell culture systems. Our model shared phenotypical, morphological and molecular features of patient leukemic cells faithfully mimicking the nature of the disease. Thus, it serves as ideal fundamental basis for pharmacological studies.

Published
2018
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39. Human invariant natural killer T cells promote tolerance by preferential apoptosis induction of conventional dendritic cells.

Author

Schmid H, Ribeiro EM, Secker KA, Duerr-Stoerzer S, Keppeler H, Dong R, Munz T, Schulze-Osthoff K, Hailfinger S, Schneidawind C, and Schneidawind D

Subjects
Animals, Apoptosis, Dendritic Cells, Humans, Lymphocyte Activation, Mice, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Natural Killer T-Cells
Abstract

Graft-versus-host disease (GvHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation. We recently showed in murine studies and in vitro human models that adoptively transferred invariant natural killer T (iNKT) cells protect from GvHD and promote graft-versus-leukemia effects. The cellular mechanisms underlying GvHD prevention by iNKT cells in humans, however, remain unknown. In order to study relevant cellular interactions, dendritic cells (DC) were either generated from monocytes or isolated directly from blood of healthy donors or GvHD patients and co-cultured in a mixed lymphocyte reaction (MLR) with T cells obtained from healthy donors or transplantation bags. Addition of culture-expanded iNKT cells to the MLR-induced DC apoptosis in a cell contact-dependent manner, thereby preventing T-cell activation and proliferation. Annexin V/propidium iodide staining and image stream assays showed that CD4+CD8-, CD4-CD8+ and double negative iNKT cells are similarly able to induce DC apoptosis. Further MLR assays revealed that conventional DC (cDC) but not plasmacytoid DC (pDC) could induce alloreactive T-cell activation and proliferation. Interestingly, cDC were also more susceptible to apoptosis induced by iNKT cells, which correlates with their higher CD1d expression, leading to a bias in favor of pDC. Remarkably, these results could also be observed in GvHD patients. We propose a new mechanism how ex vivo expanded human iNKT cells prevent alloreactivity of T cells. iNKT cells modulate T-cell responses by selective apoptosis of DC subsets, resulting in suppression of T-cell activation and proliferation while enabling beneficial immune responses through pDC.

Published
2022
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40. MAT2A as Key Regulator and Therapeutic Target in MLL r Leukemogenesis.

Author

Secker KA, Bloechl B, Keppeler H, Duerr-Stoerzer S, Schmid H, Schneidawind D, Jeong J, Hentrich T, Schulze-Hentrich JM, and Schneidawind C

Abstract

Epigenetic dysregulation plays a pivotal role in mixed-lineage leukemia ( MLL) pathogenesis, therefore serving as a suitable therapeutic target. S-adenosylmethionine (SAM) is the universal methyl donor in human cells and is synthesized by methionine adenosyltransferase 2A (MAT2A), which is deregulated in different cancer types. Here, we used our human CRISPR/Cas9- MLL -rearranged (CRISPR/Cas9- MLL r) leukemia model, faithfully mimicking MLL r patients' pathology with indefinite growth potential in vitro , to evaluate the unknown role of MAT2A. Comparable to publicly available patient data, we detected MAT2A to be significantly overexpressed in our CRISPR/Cas9- MLL r model compared to healthy controls. By using non- MLL r and MLL r cell lines and our model, we detected an MLL r-specific enhanced response to PF-9366, a new MAT2A inhibitor, and small interfering (si) RNA-mediated knockdown of MAT2A , by alteration of the proliferation, viability, differentiation, apoptosis, cell cycling, and histone methylation. Moreover, the combinational treatment of PF-9366 with chemotherapy or targeted therapies against the SAM-dependent methyltransferases, disruptor of telomeric silencing 1 like (DOT1L) and protein arginine methyltransferase 5 (PRMT5), revealed even more pronounced effects. In summary, we uncovered MAT2A as a key regulator in MLL leukemogenesis and its inhibition led to significant anti-leukemic effects. Therefore, our study paves the avenue for clinical application of PF-9366 to improve the treatment of poor prognosis MLL r leukemia.

Published
2020
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