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: 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 arc 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: 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: 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.

Abstract: The present invention pertains to methods for classifying tumorous diseases based on their specific genomic DNA methylation profile. The invention provides a method that allows for a classification of a tumor sample obtained from a patient by analysing a multitude, preferably genome wide, collection of CpG positions by comparison to a classification rule derived from a set of methylation data acquired from pre-classified tumor species. The invention is in particular useful for classifying brain tumor samples since brain tumors are characterized by a large variety of distinct tumor species which have different prognostic values and require in the clinic a for each species developed treatment regime.

Abstract: The present invention relates to modulators, in particular inhibitors, of 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 mammal. The present invention further relates to screening methods in order to identify these modulators, the use of modulators as identified in the diagnosis of these diseases, as well as kits, comprising materials for performing the methods according to the present invention.

Abstract: The present invention pertains to a method for detecting antigen presentation via antigen presenting molecules such as major histocompatibility complex (MHC) class I or II. The invention deploys a first binding agent specific for the antigen epitope and a second binding agent specific for the antigen presenting molecule. The binding agents of the invention are coupled to proximity probes which upon antigen presentation elicit a detectable signal. The method of the invention allows detecting antigen presentation via MHC in-vitro and in a tissue sample in-situ. Thus the method of the present invention finds application as a new diagnostic tool, for example in the diagnosis of various diseases such as infectious diseases, immunological disorders, in particular autoimmune diseases, and proliferative disorders such as cancer.

Abstract: For the combinatorial synthesis of molecule libraries, substances are embedded in a matrix consisting of a first solvent thereby forming transport units in a solid state of aggregation at a temperature of less than 90° C. and wherein after application to a support, the physical environment of the transport units is modified by the application of a physical process such as a laser printer whereby the substances in the transport units are linked to the support.

Abstract: A sensor means is employed to sense a distance to the surface of a subject to be examined, so that a range image may be acquired. Intensity information may be acquired alongside the distance information. The distance information and intensity information may be evaluated to track the pose of the sensor means relative to the surface of the subject to be examined, so that anatomical data related to said subject may be displayed as seen from the position and/or orientation of the sensor means or display means. By moving the sensor means or display means along the surface of the subject to be examined, such as a patient in a hospital environment, the user hence gets the impression of being able to look directly into the human body.