Abstract: Disclosed is a method for high-throughput detection of genome-wide modifications in a nucleic acid genome obtained from a cell or tissue caused by the activity of a designer nuclease comprising the following steps: a) Extraction of the genomic DNA from cells that were exposed to a designer nuclease under conditions which allow the designer nuclease to introduce a DNA double-strand break (DSB) in the genomic DNA of the cell, b) fragmentation of the nucleic acid to obtain random fragments, c) performing an end repair in order to obtain blunt ends, d) ligation with a linker comprising a sequence complementary to a so called “linker primer”, e) performing a first nucleic acid amplification reaction with a “linker primer” and a so called “ON-target primer”, whereby one primer is located upstream and one primer is located downstream of the on-target site, wherein at least one decoy primer is present in the reaction mixture, f) performing a second nucleic acid amplification reaction whereby so called “nested prim

Abstract: The present invention relates to a nucleic acid molecule which encodes a splice variant of the human P2RX7 receptor, and nucleic acid molecules derived therefrom, a recombinant vector containing said nucleic acid molecules, a host containing said recombinant vector, a polypeptide encoded by said nucleic acid molecules, a host cell expressing said polypeptide, a binding molecule binding to said polypeptide, a pharmaceutical composition comprising said binding molecule, a method for the production of the isolated polypeptide, and other methods and uses in connection therewith.

Abstract: The present invention provides novel compounds that target thrombocyte activity or aggregation capacity through cellular components for the treatment of diseases associated with Non-Alcoholic Fatty Liver Disease (NAFLD). The invention provides these compounds for treating non-alcoholic steatohepatitis (NASH), a progressed stage of NAFL (non-alcoholic fatty liver), in order to avoid the development of liver cirrhosis and Hepatocellular Carcinoma (HCC). Further provided are pharmaceutical compositions, comprising the compounds of the invention, and methods for screening new NASH therapeuticals.

Abstract: The present invention relates to oligonucleotide inhibitors of the TSC22D4 activity or expression and their uses for the prevention, treatment, and/or regulation of insulin resistance, metabolic syndrome and/or diabetes and/or for improving insulin sensitivity in a mammal.

Abstract: The present invention provides a novel class of dithiocarbamate-metal complexes and their uses in medicine. Also provided by the invention are combinations and pharmaceutical compositions, comprising a dithiocarbamate (or thiuram disulphide) such as disulfiram and cyclodextrin, with a source of a heavy metal. Surprisingly, the inventors found a synergistic potentiation of the anti-tumor effect, when a dithiocarbamate/heavy metal mixture was combined with a cyclodextrin. The compounds and combination of the invention are particularly useful in the treatment of tumor diseases, and other disorders. Provided are the compounds, combination, pharmaceutical compositions and kits, as well as methods for the preparation of the combinations of the invention.

Abstract: The present disclosure provides immunogenic compositions, such as vaccines, including DNA vaccines, and uses thereof, e.g., which include an annexin core domain to mediate efficient antigen delivery and antigen presentation in order to induce an antigen-specific immune response and/or to treat or prevent infectious diseases and/or cancer.

Abstract: The present invention pertains to antigen recognizing constructs against tumor specific proteasome splicing variants. The invention in particular provides novel T cell receptor (TCR) based molecules which are selective and specific for tumor cells carrying antigenic epitopes generated by proteasome peptide splicing of tumor specific antigens. The TCRs of the invention, and antigen binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of proliferative diseases, preferably for the treatment of cancer. Further provided are nucleic acids encoding the antigen recognizing constructs of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen recognizing constructs and pharmaceutical compositions comprising the compounds of the invention.

Abstract: The present invention pertains to a novel cell based tumor vaccine platform. The invention provides a method for modifying antigen presenting cells (APCs) to present both MHC class I and/or MHC class II peptides in context of improved peptide presentation protein complexes in order to increase activation of a patient's immune response. In this invention, an MHC II mRNA dendritic cell based vaccine platform was developed to activate CD4+T cells in patients and to enhance the anti-tumor response. The invariant chain (Ii) was modified and the semi-peptide CLIP was replaced with an MHCII binding peptide sequences of tumor associated antigens. These chimeric MHC II constructs are presented by APCs and induce proliferation of tumor specific CD4+T cells. The invention provides the constructs, proteins, nucleic acids, recombinant cells, as well as medical applications of these products.

Abstract: The present disclosure provides a novel method for treating pancreatic cancer and pancreatitis in which a combination of a dopamine receptor antagonist (pimozide, haloperidol, and/or L-741,626), 2-deoxy-D-glucose and atorvastatin are used, optionally in combination with gemcitabine.

Abstract: An integrative pharmacokinetic/pharmacodynamics (PK/PD) ESA-EpoR mathematical model calculates the binding behavior of erythropoiesis stimulating agents (ESA). The invention provides methods for the determining of ESA binding sites in cells or patients suffering from anemia. Knowing the amount of ESA binding sites enables the clinical practitioner to optimize the dosage regimen during a treatment of anemia, in particular in patients suffering from a cancerous disease. Further provided are methods for screening ESAs which have a higher specificity for cells strongly expressing the EPO receptor such as colony forming units-erythroid (CFU-E) cells, and not to cells with a low level of EPO receptor cell surface expression, which is the case in cancer cells. Also provided is a computer implemented method, comprising the use of the mathematical model of the invention.

Abstract: The present invention relates to oligonucleotide inhibitors of the TSC22D4 activity or expression and their uses for the prevention, treatment, and/or regulation of insulin resistance, metabolic syndrome and/or diabetes and/or for improving insulin sensitivity in a mammal.

Abstract: An in vitro method for the diagnosis, prognosis, stratification and/or monitoring of colorectal cancer in a subject includes detecting the level of AREG, CEA, HGF-receptor, ErbB4-Her4, CD69, PSA, EMMPRIN, and INF-gamma biomarkers in a biological sample of the subject. In an embodiment, the subject is administered a treatment when a differential level of the biomarkers compared to a healthy control or a reference value is indicative for the presence of colorectal cancer in the subject.

Abstract: The present disclosure relates to a binding molecule binding to L1, which is capable of binding to the same L1 epitope recognized by the monoclonal antibody L1-OV52.24, and/or which competes with the monoclonal antibody L1-OV52.24 for binding to L1, wherein the variable part of the light chain of L1-OV52.24 comprises the sequence according to SEQ ID No: 1 or wherein the light chain is encoded by SEQ ID No: 3, and wherein the variable part of the heavy chain of L1-OV52.24 comprises the sequence according to SEQ ID No: 2 or wherein the heavy chain is encoded by SEQ ID No: 4, nucleic acids encoding the binding molecules, uses thereof and pharmaceutical compositions comprising the binding molecules.

Abstract: The present invention provides a novel method for labelling nucleic acid probes. The method uses a ligase catalysed reaction to connect a nucleic acid probe with pre-prepared nucleic acid label carrier molecules under the presence of a stabilizing complementary splint oligonucleotide. The method allows for an easy, cheap and fast labelling of multiple probes with multiple different labels. In this way, the costs and effort for the generation of single molecule Fluorescent In Situ Hybridization (smFISH) assays was significantly reduced. The invention further provides methods for the generation of FISH libraries and labelling kits comprising the novel tools of the invention.

Abstract: A method for estimating an optical property of a tissue (10) from a photoacoustic image (20) of the tissue (10) or parts thereof (12) using a machine learning algorithm, wherein the photoacoustic image (20) is obtained with a photoacoustic setup (30) and wherein the machine learning algorithm is configured to infer the optical property at least at one domain of the photoacoustic image (20) by means of a descriptor for said at least one domain, wherein at least part of the photoacoustic image (20) is partitioned in a plurality of domains (22) with respect to at least one parameter, wherein the at least one parameter corresponds to a physical property of the tissue (10), and wherein the variation of the at least one parameter within each domain is limited to a pre-determined value, such that each domain corresponds to a limited range of said physical property of the tissue (10), and a descriptor is determined for each of said at least one domain, wherein the descriptor for a given domain (V) comprises informati

Abstract: The present invention relates to the use of Rspondins, particularly Rspondin2 (Rspo2) or Rspondin3 (Rspo3) or Rspondin nucleic acids, or regulators or effectors or modulators of Rspondin, e.g. Rspo2 and/or Rspo3 to promote or inhibit angiogenesis and/or vasculogenesis, respectively. The invention is based on the demonstration that Rspo3 and Rspo2 are angiogenesis promoters, and the identification of Rspo2 and 3 as positive regulators of vascular endothelial growth factor (VEGF). These results indicate a major role for Rspondins, particularly Rspo3 and/or Rspo2 in the signaling system during angiogenesis. The invention also relates to the use of regulators or effectors or modulators of Rspondin3, including agonists and antagonists, in the treatment of conditions where treatment involves inhibiting or promoting angiogenesis and/or vasculogenesis.

Abstract: A parvovirus characterized by a CpG-enriched genome, wherein the genome contains at least 2 additional CpG inserts that are not present in the wild type genome is described as well as the use of said parvovirus, e.g., a parvovirus based on parvovirus H1, LuIII, Mouse minute virus (MMV), Mouse parvovirus (MPV), Rat minute virus (RMV), Rat parvovirus (RPV), Rat virus (RV), vectors based on the foregoing viral species, and/or cells capable of actively producing the foregoing viral species for the preparation of a pharmaceutical composition, e.g., for the treatment of cancer, preferably pancreas carcinoma, hepatoma or lymphoma.

Abstract: The present invention relates to a method for identifying a compound that modulates the interaction of an annexin core domain with a receptor selected from the group of C-type lectin receptors and LRP-1 in a cell, and uses thereof in autoimmune and/or cancer therapy.

Abstract: The present invention discloses microRNAs (miR) involved in the regulation of the lipid and glucose metabolism. Several conserved miR molecules were found as direct targets of the glucocorticoid hormone/glucocorticoid receptor signaling axis. Hence, the present invention pertains to inhibitors of these miRs—such as antimiRs and blockmiRs—as well as isolated miR molecules or miR expression constructs for the treatment or prevention of metabolic disorders caused by deregulated glucocorticoid signaling, such as insulin resistance, the metabolic syndrome, obesity and/or diabetes type II. Particular preferred embodiments of the invention pertain to antagonists or agonists of a miR of the conserved miR-379-410 cluster, particularly of miR-379.

Abstract: The present invention relates to novel amino acid sequences of peptides derived from HPV16 that are able to bind to MHC complexes of class II, and elicit an immune response. The present invention further relates to pharmaceutical products, such as vaccines and T-cells, based on said epitopes.