A5036296550- CAR-T cell therapy research
- Cancer Research and Treatments
- Biomedical Ethics and Regulation
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Immunotherapy and Immune Responses
- HER2/EGFR in Cancer Research
- Virus-based gene therapy research
- Systemic Lupus Erythematosus Research
- Protein purification and stability
- Cytokine Signaling Pathways and Interactions
- Toxin Mechanisms and Immunotoxins
- Immune Response and Inflammation
- interferon and immune responses
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Radiopharmaceutical Chemistry and Applications
- Carbohydrate Chemistry and Synthesis
- Cell Adhesion Molecules Research
- Glycogen Storage Diseases and Myoclonus
- T-cell and B-cell Immunology
- Muscle and Compartmental Disorders
- Neuroscience and Neuropharmacology Research
- Adolescent and Pediatric Healthcare
- Allergic Rhinitis and Sensitization
- Tryptophan and brain disorders
Charité - Universitätsmedizin Berlin
2009-2024
Humboldt-Universität zu Berlin
2024
Freie Universität Berlin
2024
University of Stuttgart
2012-2023
Immatics Biotechnologies (Germany)
2020-2023
Inserm
2023
Université de Tours
2023
Centre d'Étude des Pathologies Respiratoires
2023
University of Salzburg
2021
Association for Language Learning
2015
Fusion to an IgG Fc region is established strategy extend the half-life of therapeutic proteins. Most fusion proteins, however, do not achieve long IgGs. Based on findings that scFv-Fc proteins exhibit a shorter than corresponding molecules, we performed comparative study different antibody-derived We could confirm single-chain Fv (scFv) and diabody (scDb) molecules yields in with substantially extended half-lives compared versions. However, even size similar IgG, e.g., scDb-Fc, did have as...
Abstract Background Tumour necrosis factor (TNF) is a pleiotropic cytokine and master regulator of the immune system. It acts through two receptors resulting in often opposing biological effects, which may explain lack therapeutic potential obtained so far multiple sclerosis (MS) with non-receptor-specific anti-TNF therapeutics. Under neuroinflammatory conditions, such as MS, TNF receptor-1 (TNFR1) believed to mediate pro-inflammatory activities associated TNF, whereas receptor-2 (TNFR2)...
The frequent activation of HER3 signaling as a resistance mechanism to EGFR-targeted therapy has motivated the development combination therapies that block more than one receptor tyrosine kinase. Here, we have developed novel tetravalent, bispecific single-chain diabody-Fc fusion protein targeting EGFR and (also known ErbB3) integrates antigen-binding sites humanized version cetuximab well recently anti-HER3 antibody, IgG 3-43. This antibody combines binding neutralizing properties parental...
Therapeutics that block tumor necrosis factor (TNF), and thus activation of TNF receptor 1 (TNFR1) TNFR2, are clinically used to treat inflammatory diseases such as rheumatoid arthritis, bowel disease psoriasis. However, TNFR1 TNFR2 work antithetically balance immune responses involved in diseases. In particular, promotes inflammation tissue degeneration, whereas contributes modulation regeneration. We, therefore, have developed the monovalent antagonistic anti-TNFR1 antibody derivative...
Background Selective inhibition of TNFR1 signaling holds the potential to greatly reduce pro-inflammatory activity TNF, while leaving TNFR2 untouched, thus allowing for cell survival and tissue homeostasis. ATROSAB is a humanized antagonistic anti-TNFR1 antibody developed treatment inflammatory diseases. Methodology/Principal Findings The epitope resides in N-terminal region covering parts CRD1 CRD2. By site-directed mutagenesis, we identified Arg68 His69 as important residues binding....
Abstract IMA101 is an actively personalized, multi-targeted adoptive cell therapy (ACT), whereby autologous T cells are directed against multiple novel defined peptide-HLA (pHLA) cancer targets. HLA-A*02:01-positive patients with relapsed/refractory solid tumors expressing ≥1 of 8 predefined targets underwent leukapheresis. Endogenous specific for up to 4 were primed and expanded in vitro. Patients received lymphodepletion (fludarabine, cyclophosphamide), followed by T-cell infusion low-dose...
Binding of a therapeutic protein to long-circulating plasma can result in strongly extended half-life. Among these proteins, albumin and immunoglobulins are special interest because their exceptionally long half-life, which is great extent determined by recycling through the neonatal Fc receptor (FcRn). Many strategies have been established employing reversible binding albumin, e.g. using an albumin-binding domain from streptococcal G. We show here that half-life recombinant antibody...
Multivalent mono- or bispecific antibodies are of increasing interest for therapeutic applications, such as efficient receptor clustering and activation, dual targeting approaches. Here, we present a novel platform the generation Ig-like molecules, designated diabody-Ig (Db-Ig). The antigen-binding site Db-Ig is composed diabody in VH-VL orientation stabilized by fusion to antibody-derived homo- heterodimerization domains, e.g., CH1/CL heavy chain domain 2 IgE (EHD2) IgM (MHD2), further...
Abstract Objective Analysis of the histopathologic features hip arthritis in patients with ankylosing spondylitis (AS) has revealed accumulation infiltrating mononuclear cells bone end plate and presence hyaline articular cartilage that is not found areas total destruction. This study was undertaken to assess whether chondrocytes attract lymphocytes from AS have potential directly stimulate T an HLA‐restricted manner. Methods Human HLA–B27+ cell lines, specific for Epstein‐Barr virus–derived...
Dimeric assembly of antibody fragments and other therapeutic molecules can result in increased binding improved bioactivity. Here, we investigated the use IgM heavy chain domain 2 (MHD2) as covalently linked homodimerization module. Fusion single-chain fragment variable (scFv) directed against epidermal growth factor receptor (EGFR) human to N- and/or C-terminus MHD2, respectively, resulted with single or dual specificity for tumor cells. Bispecific tetravalent were further generated by...
Selective inhibition of tumor necrosis factor (TNF) signaling through the proinflammatory axis TNF-receptor 1 (TNFR1) while leaving pro-survival and regeneration-promoting signals via TNFR2 unaffected is a promising strategy to circumvent limitations complete TNF action by approved anti-TNF drugs. A previously developed humanized antagonistic TNFR1-specific antibody, ATROSAB, showed potent TNFR1-mediated cellular responses. Because parental mouse antibody H398 possesses even stronger...
The development of alternative therapeutic strategies to tumor necrosis factor (TNF)-blocking antibodies for the treatment inflammatory diseases has generated increasing interest. In particular, selective inhibition TNF receptor 1 (TNFR1) promises a more precise intervention, tackling only pro-inflammatory responses mediated by while leaving regenerative and pro-survival signals transduced TNFR2 untouched. We recently monovalent anti-TNFR1 antibody fragment (Fab 13.7) as an efficient...
Seasonal exposure to birch pollen (BP) is a major cause of pollinosis. The specific role Toll-like receptor 4 (TLR4) in BP-induced allergic inflammation and the identification key factors extracts (BPE) initiating this process remain be explored. This study aimed examine (i) importance TLR4 for dendritic cell (DC) activation by BPE, (ii) extent contribution BPE-derived lipopolysaccharide (LPS) other potential adjuvant(s) (iii) relevance TLR4-dependent BPE-stimulated DCs initiation an...
IZI-06.1 is a humanized anti-TNFR1 single-chain fragment variable (scFv) that selectively inhibits binding of tumor necrosis factor (TNF) and lymphotoxin alpha to receptor 1 (TNFR1) but not TNFR2. Recently, was converted into fully human IgG1 antibody (ATROSAB) for the treatment inflammatory diseases. Here, we compare bivalent ATROSAB with monovalent scFv-human serum albumin (HSA) fusion protein lacking any antibody-associated effector functions possessing approximately only half molecular...
Chronic nonresolving inflammatory syndrome is a major disease feature in myeloproliferative neoplasms (MPNs). Systemic inflammation promotes the growth of JAK2-V617F+ hematopoietic stem cell clone and associated with constitutive symptoms (eg, fever, cachexia, fatigue). Therefore, it being discussed whether anti-inflammatory therapy, addition to well-established JAK inhibitor may be beneficial control symptoms. Moreover, effective microenvironment contribute prevent transformation into...
Chronic inflammatory conditions during peritoneal dialysis (PD)-treatment lead to the impairment of tissue integrity. The resulting structural and functional reorganization membrane diminishes ultrafiltration rate thereby enhances mortality by limiting effectiveness over time. Tumour necrosis factor (TNF) its receptors TNFR1 TNFR2 are key players processes. To date, role in damage PD-treatment is completely undefined. In this study, we used an acute PD-mouse model investigate on...
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