Abstract: A method is for treatment of a disease associated with genotoxic stress-induced inhibitor of nuclear factor-?B kinase/nuclear factor kappa-light chain enhancer of activated B cells (IKK/NF-?B) signaling. The method can include administering a compound to a subject having a cancer exhibiting genotoxic stress induced IKK/NF-?B activation.

Abstract: The invention relates to a xanthine derivative defined by chemical formula I or a salt thereof, its use as a medicament, especially for use in the treatment of serotonin-related diseases or disorders, and a pharmaceutical preparation comprising the xanthine derivative. The novel xanthine compounds are capable of inhibiting tryptophan hydroxylases (TPH) involved in the biosynthesis of serotonin and are effective in influencing the serotonin level in the body.

Abstract: The present invention relates to the field of immunotherapy, in particular, to adoptive T cell therapy, T cell receptor (TCR) gene therapy and vaccination. The invention provides a method for preparing a nucleic acid encoding the TCR alpha chain construct (TRA) and TCR beta chain construct (TRB) of a TCR construct specific for an epitope from an antigen presented on major histocompatibility complex (MHC), comprising contacting T cells isolated from a donor with a library of artificial antigen presenting cells (APC) comprising cells expressing all MHC I or MHC II alleles present in the donor, preferably, in K562 cells. The TCR construct can be expressed in a T cell, which is useful for adoptive T cell therapy, e.g., of cancer, viral infections or autoimmune diseases. The invention further provides a method for identifying the epitope recognized by said TCR. Immunogenic epitopes recognized by said TCRs can be used to develop vaccine formulations to induce antigen-specific T cell immunity in patients.

Abstract: The present invention relates to the field of genetic engineering, in particular, to a transposon-based transfection kit suitable for transfection of primary cells, such as T cells, comprising mRNA encoding a transposase, or reagents for generating mRNA encoding said transposase, as well as minicircle DNA comprising the transposon. The invention also relates to a nucleic acid, preferably, a DNA minicircle, comprising a transposon, wherein the transposon encodes a protein and at least one miRNA, wherein the sequences encoding the miRNA are located in an intron and expression of the protein and the miRNA is regulated by the same promoter. The invention also provides a population of cells obtainable with the method of the invention. Methods of transfection are also provided, as well as medical use, e.g. in immunotherapy, in particular, in adoptive T cell therapy or T cell receptor (TCR) or chimeric antigen receptor (CAR) gene therapy.

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: A method of treating a medical disorder associated with the presence of pathogenic B cells expressing B cell maturation antigen (BCMA), the method comprising administering to a subject an isolated antibody or antibody fragment comprising specific VH and VL domain complementary determining region (CDR) sequences, wherein the antibody or fragment thereof specifically binds an epitope of the extracellular domain of CD269 (BCMA).

Abstract: The present invention relates to the field of immunotherapy, in particular adoptive T cell therapy or T cell receptor (TCR) gene therapy of cancer. The invention provides a nucleic acid encoding at least one T cell receptor alpha chain construct and/or TCR beta chain construct of a TCR construct capable of specifically binding to an epitope from NY-ESO-1 (also designated CTAG-1) in complex with a human MHC, wherein the TCR alpha chain construct and/or the TCR beta chain construct comprises a complementarity determining region 3 (CDR3) having at least 90% sequence identity to an amino acid selected from SEQ ID NO: 1-20. The invention provides TCR constructs restricted to an epitope from NY-ESO-1 presented on MHC I, and, for the first time, TCR constructs restricted to an epitope from NY-ESO-1 presented on MHC II molecules, and thus enables a combined adoptive T cell therapy with both recombinant CD4+ and re-combinant CD8+ T cells.

Abstract: The invention relates to a xanthine derivative defined by chemical formula I or a salt thereof, its use as a medicament, especially for use in the treatment of serotonin-related diseases or disorders, and a pharmaceutical preparation comprising the xanthine derivative. The novel xanthine compounds are capable of inhibiting tryptophan hydroxylases (TPH) involved in the biosynthesis of serotonin and are effective in influencing the serotonin level in the body.

Abstract: The invention relates to antibodies or antibody fragments that bind CD269 (BCMA), thereby disrupting the interaction between CD269 and its native ligands (BAFF and APRIL), and their use in the treatment of plasma cell-mediated diseases such as multiple myeloma and autoimmune diseases.

Abstract: An antisense oligonucleotide comprising a sequence targeted to the 3? untranslated region (3? UTR) of the TNFAIP3 (A20) transcript and its use as a medicament, for example in the treatment of cancer or an autoimmune disease.

Abstract: The invention relates to a xanthine derivative defined by chemical formula I or a salt thereof, its use as a medicament, especially for use in the treatment of serotonin-related diseases or disorders, and a pharmaceutical preparation comprising the xanthine derivative. The novel xanthine compounds are capable of inhibiting tryptophan hydroxylases (TPH) involved in the biosynthesis of serotonin and are effective in influencing the serotonin level in the body.

Abstract: The present invention relates to a method for the production of novel T-cell receptors (TCR) which provide a reduced risk of adverse events in immune therapy, specifically in adoptive T cell transfer. The TCRs produced according to the method of the invention are specific for tumor cells and do not react with healthy tissue. Furthermore provided are nucleic acids encoding the TCR of the invention, vectors and host cells comprising the TCRs of the invention as well as their use is the treatment of tumorous diseases.

Abstract: The present invention is directed to a high affinity T cell receptor (TCR) against a tumor-associated antigen, an isolated nucleic acid molecule encoding the same, a T cell expressing the TCR, and a pharmaceutical composition for use in the treatment of diseases involving malignant cells expressing the tumor-associated antigen.

Abstract: Disclosed are genetically modified human pancreatic progenitor cells having an exogenous nucleic acid molecule encoding TGIF2, for use as a medicament in the treatment of a subject with diabetes. In addition methods for the production of such cells are described. Also disclosed is an expression vector encoding TGIF2 for use as a medicament in the treatment of a subject with diabetes.

Abstract: The present invention relates to the field of analysis of the three-dimensional structure of the genome, i.e., for genome architecture mapping (GAM). The invention provides a method of determining spatial proximity of a plurality of nucleic acid loci in a compartment such as the cell nucleus, by exploiting their co-segregation amongst fractions of that compartment, identified upon separation of the nucleic acid loci from each other depending on their localization in the compartment to obtain a collection of fractions, e.g., by cryo-sectioning or cryo-milling the compartment; determining the presence or absence of the plurality of loci in the fractions; and determining the co-segregation of the plurality of loci. Co-segregation may then be analysed with statistical methods to determine spatial proximity. The method can be used e.g., for determining physical distance between a plurality of loci; and mapping loci and/or genome architecture, e.g.

Abstract: The present invention provides compounds (n-3 PUFA derivatives) of formula (I): that modulate conditions associated with cardiac damage, especially cardiac arrhythmias.

Abstract: The present invention pertains to novel high avidity antigen recognizing constructs, such as antibodies or T cell receptors, which specifically bind to the melanoma associated antigen (MAGE) A1. The constructs of the invention are particularly useful for the diagnosis, prevention or therapy of tumorous diseases which are characterized by the specific expression of the MAGE-A1 antigen. Furthermore provided are nucleic acids, vectors and host cells—such as CD4 or CD8 positive T cells—which encode, comprise or present the antigen recognizing constructs of the invention. The invention thus provides new means for immune therapy, specifically adoptive T cell therapy, for treating cancer.

Abstract: The invention relates to a xanthine derivative defined by chemical formula I or a salt thereof, its use as a medicament, especially for use in the treatment of serotonin-related diseases or disorders, and a pharmaceutical preparation comprising the xanthine derivative. The novel xanthine compounds are capable of inhibiting tryptophan hydroxylases (TPH) involved in the biosynthesis of serotonin and are effective in influencing the serotonin level in the body.

Abstract: The present invention provides compounds (n-3 PUFA derivatives) of formula (I): that modulate conditions associated with cardiac damage, especially cardiac arrhythmias.

Abstract: The present invention is directed to an aptamer comprising or consisting of the nucleic acid sequence of SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 3 and/or a nucleic acid sequence being at least 80% identical to one of SEQ ID No. 1, 2 and 3 for use in therapy and/or diagnosis of autoimmune diseases, wherein the autoimmune disease is cardiomyopathy, dilated cardiomyopathy (DCM), peripartum cardiomyopathy (PPCM), idiopathic cardiomyopathy, Chagas' cardiomyopathy, Chagas' megacolon, Chagas' megaesophagus, Chagas' neuropathy, benign prostatic hyperplasia, scleroderma, psoriasis, Raynaud syndrome, pre-eclampsia, kidney allograft rejection, myocarditis, glaucoma, hypertension, pulmonary hypertension, malignant hypertension, and/or Alzheimer's disease.