A5052984671- Monoclonal and Polyclonal Antibodies Research
- Chronic Lymphocytic Leukemia Research
- T-cell and B-cell Immunology
- Cell Adhesion Molecules Research
- Immunodeficiency and Autoimmune Disorders
- Immunotherapy and Immune Responses
- HER2/EGFR in Cancer Research
- Complement system in diseases
- Advanced Biosensing Techniques and Applications
- Galectins and Cancer Biology
- Immune Cell Function and Interaction
- Blood groups and transfusion
- Biosimilars and Bioanalytical Methods
- Cell death mechanisms and regulation
- Click Chemistry and Applications
- Botulinum Toxin and Related Neurological Disorders
- Parkinson's Disease Mechanisms and Treatments
- Protein purification and stability
- Glycosylation and Glycoproteins Research
- Neurological disorders and treatments
Uppsala University
2014-2024
Science for Life Laboratory
2015
Antibody therapy of cancer is increasingly used in the clinic and has improved patient's life expectancy. Except for immune checkpoint inhibition, mode action many antibodies to recognize overexpressed or specific tumor antigens initiate either direct F(ab')2-mediated cell killing, Fc-mediated effects such as complement-dependent cytotoxicity (CDC) antibody-dependent cell-mediated cytotoxicity/phagocytosis (ADCC/P) after binding activating Fc receptors. All are IgG isotype. The IgA isotype...
NF-κB is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within pathway a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases; 7%), which encodes IκBε, negative regulator normal B cells. Strikingly, 13 these cases carried an identical 4-bp frameshift deletion, resulting truncated...
Understanding molecular interactions on immune cells is crucial for drug development to treat cancer and autoimmune diseases. When characterizing interactions, the use of a relevant living model system important, as processes such receptor oligomerization clustering can influence binding patterns. We developed protocol enable time-resolved analysis ligand receptors suspension cells. Different cell lines weakly adhering were tethered Petri-dishes with help biomolecular anchor molecule (BAM)...
Monoclonal antibodies directed against the CD20 surface antigen on B cells are widely used in therapy of cell malignancies. Upon administration, bind to expressing and induce their depletion via cell- complement-dependent cytotoxicity or by induction direct killing. The three currently most often clinic Rituximab (RTX), Ofatumumab (OFA) Obinutuzumab (OBI). Even though these all human IgG1 subclass, they have previously been described vary considerably effector functions involved therapeutic...
Based on their mechanism of action, two types anti-CD20 antibodies are distinguished: Type I, which efficiently mediate complement-dependent cytotoxicity, and II, instead more efficient in inducing direct cell death. Several molecular characteristics these have been suggested to underlie different biological functions, one being the manner binding CD20 expressed malignant B cells. However, exact model cells is unclear. In this study, I therapeutic rituximab (RTX) ofatumumab (OFA) II antibody...
Abstract Transferrin Receptor (TfR)-mediated transcytosis across the blood-brain barrier (BBB) enables uptake of bispecific therapeutic antibodies into brain. At therapeutically relevant concentrations, bivalent binding to TfR appears reduce efficiency by receptor crosslinking. In this study, we aimed improve BBB symmetric through minimizing their ability cause We created variants previously published RmAb158-scFv8D3, where linker length between RmAb158 and mTfR-targeting scFv8D3 was...
Antibody-drug conjugates (ADC) have shown promising effects in cancer therapy by combining the target specificity of an antibody with toxicity a chemotherapeutic drug. As number therapeutic antibodies is significantly larger than those used as ADCs, there unused potential for more effective therapies. However, conjugation additional molecule to may affect interaction its target, altering association rate, dissociation or both. Any changes binding kinetics can subsequent on efficacy thus are...
Cellular receptor activity is often controlled through complex mechanisms involving interactions with multiple molecules, which can be soluble ligands and/or other cell surface molecules. In this study, we combine a fluorescence-based technology for real-time interaction analysis fluorescence quenching to create novel time-resolved proximity assay study protein-receptor on living cells. This extracts the binding kinetics and affinity two proteins if they bind in surface. One application of...
Abstract The quantification of the number targets in biological systems is an important parameter to assess suitability surface markers as for drugs, drug delivery and medical imaging. Likewise, quantifying interaction with target terms affinity binding kinetics essential during development. Commonly used approaches quantify membrane antigens on live cells are based manual saturation techniques that labour-intensive, require careful calibration generated signal do not rates. Here, we present...
Soluble aggregates are reported to be the most neurotoxic species of α-Synuclein (αSyn) in Parkinson's disease (PD) and hence a promising target for diagnosis treatment PD. However, predominantly intracellular location αSyn limits its accessibility, especially antibody-based molecules prompts need exceptionally strong soluble aggregate binders enhance their sensitivity efficacy targeting extracellular pool. In this study, we have created multivalent antibodies TetraSynO2 HexaSynO2, derived...
<h3>Background</h3> T-Cell Receptor complex (TCR) is an immune structure aimed at antigen recognition and initiation of response. It bound to three protein dimers, known as Cluster Differentiation 3 (CD3), whose role related signal transduction. Since the response precisely tuned, mobilization TCR highly regulated, undergoes several rounds positioning on cell membrane, endocytosis, recycling. This study was thus understanding kinetics recycling internalization CD3ε subunit, by targeting it...
<h3>Background</h3> Monoclonal antibodies (mAbs) have the capacity to combine targeted therapy with immune activation through recruitment of cells and complement proteins via their Fc-terminus. For treatment B-cell malignancies, mAbs targeting surface marker CD20 are well established; Rituximab, Ofatumumab Obinutuzumab being most commonly used in clinic. Even though these three all IgG1 subclass they differ effector functions, especially ability engage system for depletion. Efforts been made...