A5035399938- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- RNA Interference and Gene Delivery
- Metabolomics and Mass Spectrometry Studies
- T-cell and B-cell Immunology
- Spectroscopy Techniques in Biomedical and Chemical Research
- Microtubule and mitosis dynamics
- Glioma Diagnosis and Treatment
- Advanced biosensing and bioanalysis techniques
- Immune Response and Inflammation
- Polymer Surface Interaction Studies
- Protease and Inhibitor Mechanisms
- Extracellular vesicles in disease
- Optical Imaging and Spectroscopy Techniques
- Neuroblastoma Research and Treatments
- Dendrimers and Hyperbranched Polymers
- Cancer-related Molecular Pathways
- Nanoparticle-Based Drug Delivery
- Galectins and Cancer Biology
- Virus-based gene therapy research
- Nuclear Receptors and Signaling
- Phagocytosis and Immune Regulation
- Cancer Immunotherapy and Biomarkers
- DNA Repair Mechanisms
University Hospital Carl Gustav Carus
2015-2024
TU Dresden
2015-2024
Natural killer (NK) cells are promising effector for adjuvant immunotherapy of cancer. So far, several preclinical studies have shown the feasibility gene-engineered NK cells, which upon expression chimeric antigen receptors (CARs) redirected to otherwise cell-resistant tumors. Yet, we reasoned that efficiency an using CAR-modified critically relies on efficient migration tumor site and might be improved by engraftment a receptor specific chemokine released tumor. On basis DNAX-activation...
Abstract NK cells are emerging as new effectors for immunotherapy of cancer. In particular, the genetic engraftment chimeric Ag receptors (CARs) in is a promising strategy to redirect otherwise cell–resistant tumor cells. On basis DNAX-activation protein 12 (DAP12), signaling adaptor molecule involved signal transduction activating cell receptors, we generated type CAR targeting prostate stem (PSCA). We demonstrate this article that CAR, designated anti–PSCA-DAP12, consisting DAP12 fused...
The antitumor activity of natural killer (NK) cells can be enhanced by specific targeting with therapeutic antibodies that trigger antibody-dependent cell-mediated cytotoxicity (ADCC) or genetic engineering to express chimeric antigen receptors (CARs). Despite antibody CAR targeting, some tumors remain resistant towards NK cell attack. While the importance ICAM-1/LFA-1 interaction for is known, its impact on ADCC induced ErbB2 (HER2)-specific trastuzumab and ErbB2-CAR-mediated against breast...
Survivin, belonging to the inhibitor of apoptosis (IAP) gene family, is abundantly expressed in tumors. It has been hypothesized that Survivin facilitates carcinogenesis by inhibition resulting improved survival tumorigenic progeny. Additionally, plays an essential role during mitosis. Together with its molecular partners Aurora B, Borealin and inner centromere protein it secures bipolar chromosome segregation. However, whether increased levels contribute progression tumors inducing...
Abstract Molecular reprogramming of stromal microarchitecture by tumour-derived extracellular vesicles (EVs) is proposed to favour pre-metastatic niche formation. We elucidated the role extravesicular tissue inhibitor matrix metalloproteinase-1 (TIMP1 EV ) in pro-invasive (ECM) remodelling liver microenvironment aid tumour progression colorectal cancer (CRC). Immunohistochemistry analysis revealed a high expression TIMP1 invasion front that was associated with poor progression-free survival...
Therapeutics based on small interfering RNAs (siRNAs) offer a great potential to treat so far incurable diseases or metastatic cancer. However, the broad application of siRNAs using various nonviral carrier systems is hampered by unspecific toxic side effects, poor pharmacokinetics due unwanted delivery siRNA-loaded nanoparticles into nontarget organs, rapid renal excretion. In order overcome these obstacles, several targeting strategies chemically linked antibodies and ligands have emerged....
In glioblastoma, non-classical human leucocyte antigen E (HLA-E) and HLA-G are frequently overexpressed. HLA-E loaded with peptides derived from HLA class I contributes to inhibition of natural killer (NK) cells expression the inhibitory receptor CD94/NKG2A. We investigated whether NK expressing activating CD94/NKG2C counterpart were able exert anti-glioma effects. NKG2C+ subsets preferentially expanded by a feeder cell line engineered express an artificial disulfide-stabilized trimeric...
Application of Toll-like receptor (TLR) agonists is a promising approach to treat cancer. In particular, nucleic acid-based TLR such as short ssRNA and dsRNA molecules, which activate endosomal TLRs, can be delivered tumors by use nanoparticle delivery systems. However, systems bear unspecific side effects poor pharmacokinetics. To overcome these limitations we developed system for targeted 50 bp TLR3 agonist (Riboxxol) PSCA-positive tumor cells, consists neutravidin conjugated...
Tumor Treating Fields (TTFields) were incorporated into the treatment of glioblastoma, most malignant brain tumor, after showing an effect on progression-free and overall survival in a phase III clinical trial. The combination TTFields antimitotic drug might further improve this approach. Here, we tested with AZD1152, Aurora B kinase inhibitor, primary cultures newly diagnosed (ndGBM) recurrent glioblastoma (rGBM). AZD1152 concentration was titrated for each cell line 5–30 nM used alone or...
Delivery of siRNAs for the treatment tumors critically depends on development efficient nucleic acid carrier systems. The complexation dendritic polymers (dendrimers) results in nanoparticles, called dendriplexes, that protect siRNA from degradation and mediate non-specific cellular uptake siRNA. However, large doses are required vivo use due to accumulation nanoparticles sinks such as lung, liver, spleen. This suggests exploration targeted enhancing tumor cell specificity achieving higher...
Abstract Synthetic platforms for mimicking artificial organelles or designing multivalent protein therapeutics targeting cell surface, extracellular matrix, and tissues are in the focus of this study. Furthermore, availability a multi‐functionalized stimuli‐responsive carrier system is required that can be used sequential situ and/or post loading different proteins combined with post‐functionalization steps. Until now, polymersomes exhibit excellent key characteristics to fulfill those...
Infrared (IR) spectroscopy has the potential for tumor delineation in neurosurgery. Previous research showed that IR spectra of brain tumors are generally characterized by reduced lipid-related and increased protein-related bands. Therefore, we propose exploitation these common spectral changes recognition.Attenuated total reflection was performed on fresh specimens 790 patients within minutes after resection. Using principal component analysis linear discriminant analysis, a classification...
Background aimsNatural killer (NK) cells are promising for immunotherapy of cancer, and there ongoing efforts to improve their ex vivo expansion clinically relevant numbers. This study focused on the development a C1-, C2-, Bw4 cell immunoglobulin-like receptor (KIR) ligand NKG2A ligand-containing feeder line autonomous functional NK cells.MethodsPC3PSCA-derived expressing IL-2, 4-1BBL membrane-bound IL-15-mutDAP12 (mIL-15d) fusion protein in combinations or alone were generated used...
Abstract Glioblastoma multiforme (GBM) is the most prevalent primary brain tumor endowed with a dismal prognosis. Nowadays, immunotherapy in particular immune checkpoint blockade and therapeutic vaccines are being extensively pursued. Yet, several characteristics of GBM may impact such immunotherapeutic approaches. This includes heterogeneity, relatively low mutational load GBM, insufficient delivery antibodies to parenchyma unique immunosuppressive microenvironment GBM. Moreover, standard...
Abstract Purpose: Infrared (IR) spectroscopy has the potential for tumor delineation in neurosurgery. Previous research showed that IR spectra of brain tumors are generally characterized by reduced lipid-related and increased protein-related bands. Therefore, we propose exploitation these common spectral changes recognition. Methods: Attenuated total reflection was performed on fresh specimens 790 patients within minutes after resection. Using principal component analysis linear discriminant...