6 results on '"Uharek, Lutz"'
Search Results
2. Clinical translation and regulatory aspects of CAR/TCR-based adoptive cell therapies—the German Cancer Consortium approach.
- Author
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Krackhardt, Angela M., Anliker, Brigitte, Hildebrandt, Martin, Bachmann, Michael, Eichmüller, Stefan B., Nettelbeck, Dirk M., Renner, Matthias, Uharek, Lutz, Willimsky, Gerald, Schmitt, Michael, Wels, Winfried S., and Schüssler-Lenz, Martina
- Subjects
T cells ,CELLULAR therapy ,GENE therapy ,THERAPEUTICS ,CANCER treatment - Abstract
Adoptive transfer of T cells genetically modified by TCRs or CARs represents a highly attractive novel therapeutic strategy to treat malignant diseases. Various approaches for the development of such gene therapy medicinal products (GTMPs) have been initiated by scientists in recent years. To date, however, the number of clinical trials commenced in Germany and Europe is still low. Several hurdles may contribute to the delay in clinical translation of these therapeutic innovations including the significant complexity of manufacture and non-clinical testing of these novel medicinal products, the limited knowledge about the intricate regulatory requirements of the academic developers as well as limitations of funds for clinical testing. A suitable good manufacturing practice (GMP) environment is a key prerequisite and platform for the development, validation, and manufacture of such cell-based therapies, but may also represent a bottleneck for clinical translation. The German Cancer Consortium (DKTK) and the Paul-Ehrlich-Institut (PEI) have initiated joint efforts of researchers and regulators to facilitate and advance early phase, academia-driven clinical trials. Starting with a workshop held in 2016, stakeholders from academia and regulatory authorities in Germany have entered into continuing discussions on a diversity of scientific, manufacturing, and regulatory aspects, as well as the benefits and risks of clinical application of CAR/TCR-based cell therapies. This review summarizes the current state of discussions of this cooperative approach providing a basis for further policy-making and suitable modification of processes. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
3. Association between low uric acid levels and acute graft-versus-host disease.
- Author
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Ostendorf, Benjamin, Blau, Olga, Uharek, Lutz, Blau, Igor, and Penack, Olaf
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DISEASE risk factors ,GRAFT versus host disease ,URIC acid ,HEMATOPOIETIC stem cell transplantation ,UNIVARIATE analysis ,ANALYSIS of variance ,MORTALITY ,DISEASE relapse - Abstract
Endogenous danger signals are increasingly recognized in the pathogenesis of graft-versus-host disease (GVHD). Uric acid (UA) is a known danger signal and is released from injured cells during conditioning for allogeneic hematopoietic stem cell transplantation (HSCT), but its role in GVHD is unclear. Here, we retrospectively analyze 228 consecutive patients with malignant diseases undergoing HSCT from 10/10-HLA-matched donors. Low UA levels at the time of HSCT (day 0) were significantly associated with acute GVHD grades II-IV in univariate (HR 0.836, p = 0.0072) and multivariate analyses (HR 0.815, p = 0.0047). There was no significant association between UA levels and overall survival, non-relapse mortality, and relapse. This is the first report demonstrating a negative association between UA levels and acute GVHD. Due to the easy assessment and established pharmaceutical modification of UA, our findings are potentially clinically relevant. Confirmation in independent cohorts and further investigations into underlying mechanisms, such as reduced antioxidative capacity in hypouricemia, are warranted. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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- View/download PDF
4. Intrathecal application of donor lymphocytes in leukemic meningeosis after allogeneic stem cell transplantation.
- Author
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Neumann, Martin, Blau, Igor, Burmeister, Thomas, Tietze-Buerger, Carola, Blau, Olga, Gerbitz, Armin, Uharek, Lutz, and Thiel, Eckhard
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LYMPHOCYTES ,STEM cell transplantation ,CENTRAL nervous system ,LEUKEMIA ,GRAFT versus host disease ,HEMATOLOGY ,MENINGES - Abstract
Extramedullary relapses after allogeneic stem cell transplantation, especially within the central nervous system (CNS), are not only difficult to treat but also associated with poor outcome. Although the graft-versus-leukemia (GvL) effect is nowadays accepted and well documented, it remains controversial whether one can make use of GvL effects in immunological-restricted areas ('sanctuary sites') like the central nervous system. Here, we present data of three hematological patients suffering from isolated CNS relapse of CML or AML after allogeneic stem cell transplantation. Patients received in addition to chemotherapy intrathecal infusions of donor lymphocytes by CD14 depletion of peripheral blood mononuclear cells from the correspondent allogeneic donor. Referring to an observation period of maximum 17 months no immediate or delayed side effects could be detected. [ABSTRACT FROM AUTHOR]
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- 2011
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- View/download PDF
5. Biocompatible porous ceramics for the cultivation of hematopoietic cells.
- Author
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Berthold, Almuth, Haibel, Astrid, Brandes, Natascha, Kroh, Lothar, Gross, Ulrich, Uharek, Lutz, and Schubert, Helmut
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CERAMIC materials ,POROSITY ,SERUM albumin ,BLOOD proteins ,CELL lines ,ALUMINUM oxide ,BLOOD plasma - Abstract
Porous ceramics made of alumina and hydroxyapatite were created using a protein foaming method. Porosity and pore size distribution were successfully varied by means of chemical modification of the foaming protein Bovine serum albumin (BSA). The effectiveness of the BSA and of its chemical modifications as well as the influence of the dispersing agent were investigated using synchrotron tomography. Resulting porous ceramic materials were used as three-dimensional substrates for the cultivation of human peripheral stem cells. The cells proliferated and differentiated in culture. Five cell lines consistent with human blood cell lines were observed. [ABSTRACT FROM AUTHOR]
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- 2007
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6. Graft-vs-leukemia activity and graft-vs-host disease induced by allogeneic Th1- and Th2-type CD4+ T cells in mice.
- Author
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Zeis, Matthias, Uharek, Lutz, Hartung, Götz, Glass, Bertram, Steinmann, Jörg, and Schmitz, Norbert
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T cells , *GRAFT versus host disease , *MICE , *BONE marrow , *LEUKEMIA - Abstract
Introduction: The transfer of allogeneic lymphocytes contained in a hematopoietic stem cell graft confers an immune-mediated antileukemic effect, termed the graft-vs-leukemia (GVL) effect. Graft-vs-host disease (GVHD), the most detrimental complication of allogeneic BMT, largely resides within the same lymphocyte population. Therefore, separation of GVL- and GVH-reactions is a long-standing goal of experimental studies dealing with allogeneic transplantation of hematopoietic stem cells.Materials and methods: The objective of the current study was to assess the potential of Th1- and Th2-type CD4+ T cells in mediating GVHD and GVL effects in a fully allogeneic murine transplant model. BALB/c (H-2d) mice were given a dose of A20 (H-2d, B-cell leukemia) cells two days prior to lethal total body irradiation (TBI) and transplantation of fully mismatched (C57BL/6, H-2b) T-cell depleted (anti-Thy1.2, CD90) bone marrow (TCD-BM) cells. Graded numbers of either unmanipulated, Th1- or Th2-polarized highly enriched CD4+ donor type T cells (106 or 107) were administered 2 h posttransplant. Infusion of 106 of unmanipulated, Th1-, or Th2-primed CD4+ T cells resulted in moderate GVHD-related mortality (40%, 50%, 10%) and significantly improved long-term survival (50%, 45%, 46% surviving the observation period of 120 days) as compared to animals receiving TCD-BM alone (18%).Results: The administration of 107 unmanipulated or Th1-type CD4+ T cells given shortly after transplantation led to death of all mice within 50 days due to fatal acute GVHD. In contrast, the adoptive transfer of 107 Th2-primed CD4+ T cells resulted in significant improvement of long-term survival (80%) compared to the TCD-BM group. This powerful GVL effect was associated with a substantially lower incidence of lethal acute GVHD (10%) if compared to the results of... [ABSTRACT FROM AUTHOR]
- Published
- 2001
- Full Text
- View/download PDF
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