Marcus Odendahl

Deutsches Rotes Kreuz Blutspendedienst Nord-Ost · Experimentelle Transfusionsmedizin

T cell immunity is crucial for the control of SARS-CoV-2 infections and has been widely studied on a quantitative level. However, quality of responses, in particular of CD8⁺ T cells, has only been marginally investigated so far. Here, we isolate T cell receptor (TCR) repertoires specific for immunodominant SARS-CoV-2 epitopes restricted to common H...

T cell immunity is crucial for the control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and has been widely characterized on a quantitative level. In contrast, the quality of such T cell responses has been poorly investigated, in particular in the case of CD8+ T cells. Here, we explored the quality of SARS-CoV-2-specif...

Background: Fingolimod (FTY) applied as treatment regimen of relapsing-remitting multiple sclerosis (RRMS) induces downregulation of sphingosine-1-phosphate receptors on the lymphocytes. As a result CC chemokine receptor type 7 (CCR7) expressing lymphocytes are retained within the peripheral lymph nodes thus suppressing their accumulation into the...

Antigen‐specific T cells isolated from healthy individuals (HIs) have shown great therapeutic potential upon adoptive transfer for the treatment of viremia in immunosuppressed patients. The lack of comprehensive data on the prevalence and characteristics of leukemia associated antigen (LAA)‐specific T cells in HIs still limits such an approach for...

Background: The NK-92/5.28.z cell line (also referred to as HER2.taNK) represents a stable, lentiviral-transduced clone of ErbB2 (HER2)-specific, second-generation CAR-expressing derivative of clinically applicable NK-92 cells. This study addresses manufacturing-related issues and aimed to develop a GMP-compliant protocol for the generation of NK-...

The advent of novel strategies to generate leukemia-associated-antigen (LAA)-specific T cells for adoptive immunotherapies creates a demand for standardized good laboratory practice (GLP)-compliant enumeration assays to provide a secure clinical environment-whether it is to identify potential donors, define therapeutic doses for transplantation, or...

Cytomegalovirus (CMV) infection is a common, potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed prospectively safety and efficacy of stem cell-donor- or third-party-donor-derived CMV-specific T cells for the treatment of persistent CMV infections after allo-HSCT in a phase...

Natural killer (NK) cells are increasingly considered as immunotherapeutic agents in particular in the fight against cancers. NK cell therapies are potentially broadly applicable and, different from their T cell counterparts, do not cause graft-versus-host disease. Efficacy and clinical in vitro or in vivo expansion of primary NK cells will however...

While adoptive transfer of virus antigen specific T cells has shown to be effective in therapy of resistant recurrent viremia which is frequently associated with the lack of protective immunity following hematopoietic stem cell transplantation, the transfer of leukemia associated antigen specific (LAA) T cells is less implemented and appears to dep...

Recently, mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have been suggested as an alternative to MSCs for the treatment of various inflammatory disorders. However, while a first case report observed beneficial therapeutic effects of repeated MSC EV infusions in a patient with therapy refractory graft versus host disease (GvHD),...

Natural killer (NK) cells are an important effector cell type for adoptive cancer immunotherapy. Similar to T cells, NK cells can be modified to express chimeric antigen receptors (CARs) to enhance antitumor activity, but experience with CAR-engineered NK cells and their clinical development is still limited. Here, we redirected continuously expand...

Background aims Reactivation of cytomegalovirus (CMV) after hematopoietic stem cell transplantation remains a major cause of morbidity despite improved antiviral drug therapies. Selective restoration of CMV immunity by adoptive transfer of CMV-specific T cells is the only alternative approach that has been shown to be effective and non-toxic. We de...

While EGFRvIII appears a logical target for immunotherapy, only a subpopulation of tumor cells express EGFRvIII and immune escape has been demonstrated. ErbB2 is overexpressed in a substantial proportion of glioblastomas and has been successfully utilized in immunotherapies. Natural killer (NK) cells are the first line of defense against viral infe...

Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are threatened by potentially lethal viral manifestations like cytomegalovirus (CMV) reactivation. Because the success of today's virostatic treatment is limited by side effects and resistance development, adoptive transfer of virus-specific memory T cells derived fr...

Introduction: Recently, several groups have reported the secretion of membrane vesicles (MVs) from various cell types, including mesenchymal stromal cells (MSCs). Interest in MVs has intensified due to the rec- ognition of their role as an important component of the intracellular microenvironment. Therefore, our work aimed to characterize MSC-deriv...

have been used for vaccination of MSI+ colorectal cancer patients in a Phase I clinical trial. From a responding patient we isolated a CD8neg/CD4neg CTL clone from which we cloned an HLA-A2-restricted TGFbRIImut-specific TCR. We showed that both CD8+ and CD4+ T cells transiently redirected with this TGFbRIImut-TCR recognised colon carcinoma cell li...

Mesenchymal stromal cells (MSCs) are promising candidates for the treatment of graft-versus-host and autoimmune diseases. Here, by virtue of their immunosuppressive effects, they are discussed to exhibit inhibitory actions on various immune effector cells, including T lymphocytes that promote the underlying pathology. While it becomes apparent that...

Introduction Greiner et al. demonstrated data suggesting a promising link between CD8+ T cell responses with a specificity of NPM1mut and graft versus leukemia effect (GvL). In patients with acute myeloid leukemia (AML) who underwent hematopoietic stem cell (HSC) transplantation, effector cells of the newly established immune system are thought to...

Poster presentation: 28th Annual Scientific Meeting of the Society for Immunotherapy of Cancer (SITC) Significant progress has been made over the last decade towards realizing the potential of natural killer (NK) cells for cancer immunotherapy. NK cells can respond rapidly to transformed and stressed cells, and have the intrinsic potential to extra...

Introduction: Adoptive transfer of human bone marrow mesenchymal stromal cells (BM-MSCs) in the context of post-transplant GvHD relies on their immunosuppressive abilities, which are still not fully characterized. Recently, an important role for the CD39-CD73-adenosine pathway in mediating immunosuppression was demonstrated in Tregs. Within this pa...

In this study, we studied whether the contents of the two compartments of automatically processed cord blood (CB) units are comparable with respect to cell counts and viability and therefore suitable for clinical therapy. CB-derived stem cells are increasingly used for allogeneic transplantation. Many centres prepare the transplants by automated me...

Die durchflusszytometrische Bestimmung der Anzahl vitaler CD34⁺ Vorläufer- und Stammzellen ist in vielen Laboratorien zu einer Routineuntersuchung geworden und ihre Genauigkeit ist entscheidend für die Bestimmung der Qualität von stammzellhaltigen Produkten und für die Optimierung des Sammelns von Stammzellen nach Mobilisierung. Allerdings ist die...

Introduction: Mesenchymal stromal cells (MSCs) are emerging as novel treatment modality for a variety of diseases, among them GvHD and autoimmune diseases. Validated potency tests to assess immunosuppressive functionality to define release criteria are warranted. However, results of the mixed lymphocyte reactions (MLR), when using different donor s...

Introduction: Mesenchymal stromal cells (MSCs) are promising candidates for the treatment of GvHD and autoimmune diseases. However, MSC have been discussed to harbor the risk of malignant transformation, which may limit their clinical use and also warrants extensive quality controls for genomic stability on each single batch. Therefore, we asked wh...

Programmed death 1 (PD-1) is known as an important factor for the development of tolerogenicity. This has been proven in chronic viral infections and different tumor models. To address the role of PD-1 and its ligand programmed death ligand 1 (PD-L1) in different stages of malignant melanoma, we investigated peripheral blood and tumor tissues in re...

Cytomegalovirus (CMV) disease constitutes a serious complication after allogeneic stem cell transplantation. For the clearance of CMV, CD8+ T cells are pivotal. Here, the novel streptamer technology was used at good manufacturing practice (GMP) level for adoptive transfer of CMV-specific T cells into acute leukemia patients with recurrent high CMV...

Enumeration of CD34(+) cells in leukocyte-rich cell suspensions is important for clinical decision-making in stem cell transplantation. Single-platform flow cytometry assays offer the significant advantages of speed and reproducibility, and have therefore become the gold standard in stem cell enumeration. The clinical community has recently defined...

Background: Cytomegalovirus (CMV) disease constitutes a serious complication after allogeneic peripheral blood stem cell transplantation (allo-PBSCT). For the clearance of CMV, CD8+ T cells are pivotal. Patients after allo-PBSCT with recurrent CMV reactivation usually lack such CMV specific T cells. Conventional antiviral therapy of CMV reactivatio...

Maintenance of protective humoral immunity depends on the generation and survival of antibody-secreting cells. The bone marrow provides niches for long-term survival of plasma cells generated in the course of systemic immune responses in secondary lymphoid organs. Here, we have analyzed migratory human plasma blasts and plasma cells after secondary...

In systemic lupus erythematosus (SLE), the increased generation of memory B cells and plasma cells leads to autoimmune hypergammaglobulinemia and destructive immunoglobulin deposits in the kidneys. We undertook this study to determine the biologic mechanism driving this overactivation of the B cell compartment, which is the central issue in SLE. We...

Despite the important role immunoglobulin G (IgG)-secreting plasma cells play in memory immune responses, the differentiation and homeostasis of these cells are not completely understood. Here, we studied the differentiation of human IgG-secreting cells ex vivo and in vitro, identifying these cells by the cellular affinity matrix technology. Severa...

To investigate the distribution of peripheral B cell subpopulations of children with active and inactive systemic lupus erythematosus (SLE) compared with healthy controls. Peripheral B cell subpopulations of 11 children with SLE (6 with active and 5 with inactive disease) and 14 age matched normal healthy children were analysed. Active disease was...

Abnormalities in humoral immunity play a significant role in systemic lupus, mandating further studies in B-cell autoimmunity in this entity. Disease activity in systemic lupus erythematosus (SLE) is usually assessed with complex disease activity scores composed of a variety of different parameters. To determine whether SLE disease activity correla...

Disease activity in systemic lupus erythematosus (SLE) is usually assessed with complex disease activity scores comprising a variety of different parameters. In order to determine whether SLE disease activity correlates with abnormal B lymphocyte activity, B cell subsets were analyzed, and their relationship to clinical and humoral measures of dise...

Recent results on the biology of plasma cells have shown that these cells can survive as long as memory B cells. Possibly, such long-lived plasma cells are also involved in the production of autoantibodies. Here, we discuss the potential involvement of long-lived plasma cells in the pathogenesis of autoimmune disease and the consequences it has for...

Autoimmune phenomena may precede or accompany lymphoid malignancies, especially B-chronic lymphocytic leukemia (B-CLL). We report a patient with a 7-year history of primary (idiopathic) cold agglutinin (CA) disease in whom B-CLL subsequently developed. Immunophenotyping and single-cell reverse transcription-polymerase chain reaction (RT-PCR) were a...

A number of autoantibodies play a significant role in collagen vascular diseases and represent diagnostic markers of some of these entities. Despite increasing knowledge of these serological findings, data are limited about potential disturbances of precursor cells that finally lead to the autoantibody producing plasma cells. Recent evidence of dis...

To delineate the mechanism of the abnormalities in B cell biology found in patients with primary Sjögren's syndrome (SS). The distribution of peripheral B cell subpopulations in 21 patients with primary SS was analyzed by immunofluorescence labeling and flow cytometry. Immunoglobulin rearrangements were analyzed in single B cells isolated from the...

Im Rahmen von rheumatisch-entzündlichen Erkrankungen, insbesondere den Kollagenosen sind Autoantikörper von diagnostischer und auch ätiopathogenetischer Relevanz. Über die Zellen, die diese Autoantikörper produzieren, ist sehr wenig bekannt. Zytometrische Analysen gestatten, Zellen des Immunsystems anhand spezifischer Markermoleküle zu identifizier...

To determine whether patients with Sjögren's syndrome (SS) have abnormalities in Ig Vlambda and Jlambda gene usage, differences in somatic hypermutation, defects in selection, or indications for perturbations of B cell maturation. Individual peripheral B cells from SS patients were analyzed for their Vlambda gene usage by single-cell polymerase cha...

Objective To determine whether patients with Sjögren's syndrome (SS) have abnormalities in Ig Vλ and Jλ gene usage, differences in somatic hypermutation, defects in selection, or indications for perturbations of B cell maturation.Methods Individual peripheral B cells from SS patients were analyzed for their Vλ gene usage by single-cell polymerase c...

Objective To determine whether patients with Sjögren's syndrome (SS) have abnormalities in Ig Vλ and Jλ gene usage, differences in somatic hypermutation, defects in selection, or indications for perturbations of B cell maturation. Methods Individual peripheral B cells from SS patients were analyzed for their Vλ gene usage by single‐cell polymerase...

Background The distribution of peripheral B cell subpopulations in SLE is unknown, although a variety of humoral abnormalities are known. Objectives The phenotype and Ig heavy chain gene usage of peripheral B cell subpopulations of patients with active systemic lupus erythematosus (SLE) were examined. Methods Peripheral B cells were characterised...

In patients with active systemic lupus erythematosus (SLE), a marked B lymphocytopenia was identified that affected CD19(+)/CD27(-) naive B cells more than CD19(+)/CD27(+) memory B cells, leading to a relative predominance of CD27-expressing peripheral B cells. CD27(high)/CD38(+)/CD19(dim)/surface Ig(low)/CD20(-)/CD138(+) plasma cells were found at...

Recent studies in mice have indicated that the long-lasting specific antibody responses seen after vaccination are probably due to the existence of long-lived plasma cells. Therefore, because the maintenance of humoral immunity does not necessarily reflect continuous restimulation of long-lived memory B cells, the question arises as to what degree...

Berlin, Humboldt-Univ., Diss., 2002.