Lubomir Arseniev

Lubomir Arseniev
Hannover Medical School | MHH · Cellular Therapy Centre (CTC)

MD, PhD, MBA

About

88
Publications
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Publications

Publications (88)
Article
Full-text available
Background Immune cell dysfunction plays a central role in sepsis-associated immune paralysis. The transfusion of healthy donor immune cells, i.e., granulocyte concentrates (GC) potentially induces tissue damage via local effects of neutrophils. Initial clinical trials using standard donor GC in a strictly extracorporeal bioreactor system for treat...
Article
Full-text available
Acute myeloid leukemia (AML) patients with minimal residual disease and receiving allogeneic hematopoietic stem cell transplantation (HCT) have poor survival. Adoptive administration of dendritic cells (DCs) presenting the WT1 leukemia-associated antigen can potentially stimulate de novo T and B cell development to harness the Graft-versus-Leukemia...
Article
Die adoptive Immuntherapie ist ein vielversprechender Ansatz im Kampf gegen Krebs. Nach dem großen Erfolg und ersten Erfahrungen mit der Verwendung von CAR (chimärer Antigen-Rezeptor)-T-Zellen stehen weitere Immunzellen im Fokus der Wissenschaft. NK-Zellen sind durch ihr angeborenes Potenzial zur Vernichtung von Tumorzellen sowie virusinfizierten Z...
Article
Full-text available
Aims In the placebo-controlled, double-blind BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) 2 trial, intracoronary autologous bone marrow cell (BMC) transfer did not improve recovery of left ventricular ejection fraction (LVEF) at 6 months in patients with ST-elevation myocardial infarction (STEMI) and moderately reduced...
Article
Full-text available
In cellular immunotherapies, natural killer (NK) cells often demonstrate potent antitumor effects in high-risk cancer patients. But Good Manufacturing Practice (GMP)-compliant manufacturing of clinical-grade NK cells in high numbers for patient treatment is still a challenge. Therefore, new protocols for isolation and expansion of NK cells are requ...
Article
Clinical studies using autologous CAR T cells have achieved spectacular remissions in refractory CD19+ B cell leukaemia, however some of the patient treatments with CAR T cells failed. Beside the heterogeneity of leukaemia, the distribution and senescence of the autologous cells from heavily pretreated patients might be further reasons for this. We...
Article
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The utilization of human induced pluripotent stem cells (hiPSCs) for disease modeling and drug discovery is already reality, and several first-in-man-applications as cellular therapeutics have been initiated. Implementation of good manufacturing practice (GMP)-compliant protocols for the generation of hiPSC lines is crucial to increase the applicat...
Article
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Background and aims: The administration of ex-vivo expanded Natural killer (NK) cells as potential antitumor effector cells appears to be suitable for effector cell-based immunotherapies in high-risk cancer patients. However, the GMP-conform manufacturing of clinical-grade NK cells at sufficiently high numbers represent a great challenge. Therefor...
Article
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Aims: Intracoronary infusion of autologous nucleated bone marrow cells (BMCs) enhanced the recovery of left ventricular ejection fraction (LVEF) after ST-segment elevation myocardial infarction (STEMI) in the randomised-controlled, open-label BOOST trial. We reassessed the therapeutic potential of nucleated BMCs in the randomised placebo-controlle...
Article
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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-...
Article
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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 robustne...
Patent
In a process for preparing disinfected preparations from mammalian tissues, mammalian tissue is perfused at one step with an enzyme-free liquid antibiotic composition that includes at least one antibiotic and is contained in at least one perfusion buffer. In a step occurring after such one step, enzymatic antibiotic-free treatment of the tissue is...
Article
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The primary cutaneous T-cell lymphomas (CTCL) represent a clonal T-lymphocyte proliferation infiltrating the skin. CD30(+)T-cell lymphomas present clinically as nodules with a diameter between 1 and 15 cm, mostly in elderly patients. The role of the CD30 molecule in patients suffering from T-cell lymphomas is not completely clear yet. The signal tr...
Article
Full-text available
We assessed whether a single intracoronary infusion of autologous bone marrow cells (BMCs) can have a sustained impact on left ventricular ejection fraction (LVEF) in patients after ST-elevation myocardial infarction (STEMI). In the BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) trial, 60 patients with STEMI and successfu...
Article
Full-text available
Allogeneic haematopoietic SCT (allo-HSCT) from a matched sibling donor is a curative treatment option for patients with high-risk ALL. Congenital or acquired diseases of the donor are potentially transmissible to the recipient.1, 2 There are reports of immune thrombocytopenic purpura (ITP) after allo-HSCT associated with GVHD,3 anti-plt allo-Abs,4...
Article
In a recently published paper development of a sensitive automated “on-line” solid-phase extraction (SPE)/RP-HPLC assay for 6β-hydroxytestosterone (6β-OHT) with corticosterone as the internal standard (IS) was reported and its potential for quantification of various testosterone metabolites in culture media reflecting metabolic activity of cultured...
Article
To report on the feasibility and safety of an intravitreal injection of mononuclear cells derived from autologous bone marrow. A 43-year-old patient with very advanced atrophy of the retina and optic nerve caused by diabetic retinopathy had undergone pars plana vitrectomy with silicone oil endotamponade. Despite complete retinal attachment, vision...
Article
Between April 2005 and June 2007 in the pediatric transplantation unit - Sofia, Bulgaria 15 hematopoietic stem cell transplantations (HSCT - 13 peripheral and 2 - bone marrow) were performed by 14 patients (pts) with poor prognostic leukemia, aged median 21 years (8-55): 4 with acute myeloid leukemia (AML), 9 - acute lymphoblastic leukemia (ALL), 1...
Article
Intracoronary application of BM-derived cells for the treatment of acute myocardial infarction (AMI) is currently being studied intensively. Simultaneously, strict legal requirements surround the production of cells for clinical studies. Thus good manufacturing practice (GMP)-compliant collection and preparation of BM for patients with AMI was esta...
Article
Intracoronary transfer of autologous bone marrow cells (BMCs) may enhance recovery of left ventricular (LV) function in patients after acute myocardial infarction (AMI). However, clinical studies addressing the effects of BMCs after AMI have covered only limited time frames ranging from 3 to 6 months. The critical question of whether BMC transfer c...
Article
Freshly isolated human hepatocytes are considered as the gold standard for in vitro testing of drug candidates. Meanwhile also cryopreserved human hepatocyte suspensions are available. However, a drawback of these cells is the incalculability of attachment to the culture dish. Therefore, we established a technique freezing hepatocytes cultured on a...
Article
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Differentiation of adult bone marrow (BM) cells into nonhematopoietic cells is a rare phenomenon. Several reports, however, suggest that human umbilical cord blood (hUCB)-derived cells give rise to hepatocytes after transplantation into nonobese diabetic-severe combined immunodeficient (NOD-SCID) mice. Therefore, we analyzed the hepatic differentia...
Article
Intracoronary transfer of autologous bone marrow cells (BMCs) promotes recovery of left ventricular systolic function in patients with acute myocardial infarction. Although the mechanisms of this effect remain to be established, homing of BMCs into the infarcted myocardium is probably a critical early event. We determined BMC biodistribution after...
Article
During the last decade, hepatocyte transplantation has been suggested as a safe and potentially effective clinical option for the treatment of acute or decompensating chronic liver failure as well as for hereditary liver disease. Currently, one of the major limiting factors for clinical application is the insufficient access to suitable liver cell...
Article
Intracoronary transfer of autologous bone marrow cells (BMCs) has been shown to promote recovery of left ventricular (LV) systolic function in patients with acute myocardial infarction. (BOOST Trial; Wollert et al. Lancet, 2004, 364 141-8). Although the mechanisms of this effect remain to be established, homing of BMCs to the infarcted LV is probab...
Article
Full-text available
An active assessment of the host capacity to prevent infection during myelosuppression should be beneficial in patients receiving high-dose chemotherapy. A single dose of granulocyte colony-stimulating factor (G-CSF) (5 microg/kg) was given to 57 patients with multiple myeloma early after the completion of 85 high-dose chemotherapy (melphalan 200 m...
Article
Emerging evidence suggests that stem cells and progenitor cells derived from bone marrow can be used to improve cardiac function in patients after acute myocardial infarction. In this randomised trial, we aimed to assess whether intracoronary transfer of autologous bone-marrow cells could improve global left-ventricular ejection fraction (LVEF) at...
Article
We have investigated the contribution of intrasplenic bone marrow transplants or in vivo mobilized hematopoietic stem cells to the formation of hepatocytes in normal and injured liver. Direct intrasplenic injections of bone marrow mononuclear cells (5 x 10(5) cells), Scal+/lin- hematopoietic stem cells (5 x 10(3)) cells, and highly purified "side p...
Article
In beta-cells activation of the cyclic AMP (cAMP)-signaling cascade stimulates c-fos mRNA expression, which involves cAMP- and Ca(2+)-mediated mechanisms. To delineate potential crosstalk between both pathways at the transcriptional level we simultaneously measured c-fos promoter-driven enhanced green fluorescent protein (EGFP) expression and cytos...
Article
Background: Positive selection of CD34+ cells may be associated with an alteration of the target cells by antigen-antibody interactions and/or a selection of distinct CD34-cell subgroups within the purified cell fraction. Thus, a negative CD34 cell selection procedure (StemSep™), carried out on leukapheresis samples (LA) of patients with breast can...
Article
The potential risk of viral transmission in the setting of xenotransplantation has gained major attention. Different porcine cell types have been shown to release retroviral particles, which are infectious for human cell lines in vitro. However, there are only a few data on whether PERV (pig endogenous retrovirus) is able to infect primary human ce...
Article
Detection of residual tumor cells in BM and PBPC products has been correlated with worse outcome of breast cancer patients. Still, there is a considerable demand for studies investigating the influence of the actual tumor cell number on prognosis, as quantification routinely has been cumbersome and time consuming and, thus, was evaded. We developed...
Article
CD34+ cell enumeration is currently the most appropriate technique for hematopoietic graft quality control. At the same time, numerous CD34 mAb have become commercially available. This study was designed to compare the commonly used clones 8G12 and QBEND-10 with the new clones 581 and BIRMA-K3. All available fluorochrome conjugates were tested: FIT...
Article
High-dose chemotherapy with autologous transplantation of in vivo purged PBSC is a novel investigational approach to treating chronic myelogenous leukemia (CML) patients not responsive to conventional therapy with interferon-alpha (IFN-alpha) and not eligible for allogeneic transplantation. PBSC mobilization using either '5+2/7+3'-type chemotherapy...
Article
Full-text available
High-dose chemotherapy with autologous transplantation of in vivo purged PBSC is a new and interesting therapeutic option for CML patients not eligible for allogeneic transplantation. We investigated the feasibility and toxicity of this approach in 57 patients with Ph-positive CML. For mobilization of Ph-negative PBSC, patients were treated either...
Article
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Recent cloning of the human C3a receptor (C3aR) revealed that this receptor belongs to the large family of rhodopsin-type receptors. A unique feature of the C3aR is the large second extracellular loop comprising about 175 amino acid residues. We constructed combinatorial phage Ab libraries expressing single chain Fv Abs from BALB/c mice immunized w...
Article
48 healthy donors underwent peripheral blood stem cell (PBSC) apheresis for allogeneic transplantation beginning on day 4 of G-CSF (2 x 5 microg/kg) mobilization. In one to four (median two) large-volume mononuclear cell aphereses, a median of 55.9 x 10(9) of lymphocytes (range 21.0-109.2 x 10[9]) were collected, an amount comparable to lymphocyte...
Article
Background: Accurate electronic compensation of spectral overlapping is important for the determination of cell subsets analyzed by multicolor flow cytometry. A modification of the stepwise compensation technique with simultaneous single-step and -screen compensation is described. Materials and methods: Separate compensation controls were generated...
Article
Graft-versus-host disease (GVHD) remains the major problem to be overcome in transplantation of allogeneic haemopoietic stem cells. Using immunosuppressive prophylaxis with cyclosporin and methotrexate, moderate to severe acute GVHD develops in approximately 45% of transplant recipients with an HLA-identical sibling donor and in >75% of patients fr...
Article
Background: Transplantation of selected allogeneic or autolo-gous CD34+ cells has become a widespread method for purging of hematopoietic grafts. Specific immunoselection, based on avidin-biotin affinity with a CD34 monoclonal antibody, represents one of the commercially available techniques. Materials and Methods: Input and output of 47 CD34+ cell...
Article
BACKGROUND This Phase I/II study investigates increasingly high doses of ifosfamide combined with full dose doxorubicin chemotherapy supported with peripheral blood stem cells (PBSC) and granulocyte-colony stimulating factor (G-CSF) in patients with metastatic soft tissue sarcoma (STS).METHODS Patients with histologically proven metastatic or advan...
Article
The transplantation of allogeneic peripheral blood progenitor cells (PBPC) provides complete and sustained hematopoietic and lymphopoietic engraftment. In healthy donors, large amounts of PBPC can be mobilized with hematopoietic growth factors. However, the high content of immunocompetent T-cells in apheresis products may expose recipients of allog...
Article
Full-text available
Determinations of committed haemopoietic progenitor cells, namely CFU-GM (colony-forming unit-granulocyte/macrophage) and of CD34-expression haemopoietic cells as assessed by multiparameter flow cytometry are routine diagnostic tools in haemopoietic cell therapy. Generally, the tests are used to optimise the timing and management of cytapheresis an...
Article
Full-text available
The pathophysiological relevance of the complement split product C3a as a proinflammatory mediator is still ill defined. The expression pattern of the human C3a receptor (C3aR) can provide important clues for the role of this anaphylatoxin in inflammation. There is strong evidence for C3aR expression on basophils, and eosinophils, but additionally,...
Article
The pathophysiological relevance of the complement split product C3a as a proinflammatory mediator is still ill defined. The expression pattern of the human C3a receptor (C3aR) can provide important clues for the role of this anaphylatoxin in inflammation. There is strong evidence for C3aR expression on basophils, and eosinophils, but additionally,...
Article
The biological effects of the potent inflammatory mediator C5a, a complement split product, on human neutrophils and monocytes are limited by the rapid internalization of its specific receptor (C5aR, CD88). The C terminus of the C5aR is phosphorylated after stimulation with C5a of phorbol ester, and this phosphorylation might lead to receptor inter...
Article
An allogeneic transplantation programme using immunoselected blood progenitor and bone marrow CD34+ cells has been established. Thirteen healthy HLA-matched, MLC negative sibling donors received two doses of 5 micrograms kg-1 G-CSF (s.c. daily) for 5 days. On days 4 and 5, large-volume mononuclear cell aphereses were performed (COBE Spectra) and on...
Chapter
The transplantation of allogeneic peripheral blood progenitor cells (PBPC) could provide durable hematopoietic engraftment. In healthy bone marrow (BM) donors, large amounts of PBPC can be mobilized with hematopoietic growth factors (1–7). However, the high content of immunocompetent T cells in apheresis products may expose recipients of allogeneic...
Article
Colony forming cell (CFC) cultivation and enumeration, usually reported as CFU-GM and BFU-E growth, is still one of the conventional techniques for hematopoietic graft quality control. Reproduction of the CFC numbers is difficult by the comparison of different institutions and may also be crucial within single laboratories. Thus, the possible bias...
Article
Full-text available
Exposure of neutrophils to anaesthetic agents may alter their functional characteristics and in patients undergoing long-term sedation this may be clinically relevant. We have investigated the in vitro influence of propofol, thiopentone, methohexitone and midazolam on phorbol 12-myristate 13-acetate (PMA)-induced respiratory burst of neutrophils by...