Abstract: The invention relates to variants of interleukin-2 (IL2). In particular, the invention relates to a polypeptide comprising a mutein of human IL2 or of a functional variant of human IL2, wherein the human IL2 or functional variant thereof is substituted such that affinity for the ?? IL2 receptor complex (IL2R??) is enhanced. In one embodiment, the human IL2 or functional variant thereof is further substituted such that affinity for the ??? IL2 receptor complex (IL2???) is reduced. In one embodiment, the polypeptide activates effector T cells over regulatory T cells.

Abstract: The present invention relates to a T cell receptor (TCR) capable of binding to a PRAME peptide having the amino acid sequence SLLQHLIGL (SEQ ID NO: 1) or a portion thereof, or its HLA-A2 bound form. Also encompassed in the present invention is a nucleic acid encoding a TCR, a vector comprising the nucleic acid, and a host cell comprising the TCR, the nucleic acid sequence, or the vector. Comprised is further, a method for obtaining a TCR described herein, a pharmaceutical or diagnostic composition, and a method of detecting the presence of a cancer in a subject in vitro. Furthermore, the present invention relates to the use of a TCR, a nucleic acid and/or a vector for generating modified lymphocytes.

Abstract: The present invention is in the field of tumor immunotherapy. In particular, the present invention provides individualized cancer vaccines specific for a patient's tumor based on a transcriptome analysis in a tumor specimen of the patient for RNA transcripts which are excessively upregulated in one or more cancer cells of said patient. These individualized cancer vaccines when administered to the patient induce an immune response against tumor-associated antigens expressed in a tumor of the patient by the RNA transcripts which are excessively upregulated in one or more cancer cells of said patient. Due to the excessive upregulation of the RNA transcripts, the individualized cancer vaccines are effective for vaccination of a subject and for breaking the self-tolerance against tumor-associated antigens which are self-proteins in said subject.

Abstract: The present invention relates to novel binding agents and their use in medicine. In particular, the invention relates to binding agents such as bispecific antibodies binding human PD-L1 and binding human CD137. The invention furthermore relates to uses of the antibodies of the invention and to methods, nucleic acid constructs and host cells for producing antibodies of the invention.

Abstract: The invention relates to variants of interleukin-2 (IL2). In one embodiment, the IL2 variants activate effector T cells over regulatory T cells. In particular, the invention relates to a polypeptide comprising a mutein of human IL2 or of a functional variant of human IL2, wherein the human IL2 or functional variant thereof is substituted at at least a position having an acidic or basic amino acid residue in wild type human IL2 that contacts the alpha subunit of the ??? IL2 receptor complex (I12K???). Alternatively, the mutein of human IL2 or of a functional variant of human IL2 comprises at least (i) one or more amino acid substitutions which reduce the affinity for the alpha subunit of II_2K??? and (ii) one or more amino acid substitutions which enhance the affinity for II_2K??.

Abstract: The present invention relates to stabilization of RNA, in particular mRNA, and an increase in mRNA translation. The present invention particularly relates to a modification of RNA, in particular in vitro-transcribed RNA, resulting in increased transcript stability and/or translation efficiency. According to the invention, it was demonstrated that certain sequences in the 3?-untranslated region (UTR) of an RNA molecule improve stability and translation efficiency.

Abstract: The present invention relates to the diagnosis and treatment of diseases expressing Fibronectin Extra Domain B (EDB) such as diseases characterized by tissue remodeling and/or angiogenesis, in particular cancerous diseases, such as head and neck, brain, colorectal, lung, prostate and breast cancer. More particularly, the invention concerns peptides targeting Fibronectin Extra Domain B.

Abstract: The present disclosure provides methods for treating an individual with pancreatic cancer with an individualized cancer vaccine and a PD-1 axis antagonist.

Abstract: The present invention relates to RNA therapy and, in particular, decreasing immunogenicity of RNA. Specifically, the present invention provides methods for decreasing immunogenicity of RNA, said methods comprising modifying the nucleotide sequence of the RNA by reducing the uridine (U) content, wherein said reduction of the U content comprises an elimination of U nucleosides from the nucleotide sequence of the RNA and/or a substitution of U nucleosides by nucleosides other than U in the nucleotide sequence of the RNA. Using RNA having decreased immunogenicity allows administration of RNA as a drug to a subject, e.g. in order to obtain expression of a pharmaceutically active peptide or protein, without eliciting an immune response which would interfere with therapeutic effectiveness of the RNA or induce adverse effects in the subject.

Abstract: The present disclosure relates to methods for preparing RNA lipoplex particles for delivery of RNA to target tissues after parenteral administration, in particular after intravenous administration, and compositions comprising such RNA lipoplex particles. The present disclosure also relates to methods which allow preparing RNA lipoplex particles in an industrial GMP-compliant manner. Furthermore, the present disclosure relates to methods and compositions for storing RNA lipoplex particles without substantial loss of the product quality and, in particular, without substantial loss of RNA activity.

Abstract: The present invention relates to binding agents binding to receptors of the TNF superfamily, in particular binding agents binding to at least two different receptors of the TNF superfamily, as well as to their use in medicine. The present invention further relates to nucleic acid molecules encoding such binding agents, to cells comprising such nucleic acid molecules and to pharmaceutical compositions and kits.

Abstract: The present disclosure relates to RNA particles for delivery of RNA to target tissues after administration, in particular after parenteral administration such as intravenous, intramuscular, subcutaneous or intratumoral administration, and compositions comprising such RNA particles. The RNA particles in one embodiment comprise single-stranded RNA such as mRNA which encodes a peptide or protein of interest, such as a pharmaceutically active peptide or protein. The RNA is taken up by cells of a target tissue and the RNA is translated into the encoded peptide or protein, which may exhibit its physiological activity.

Abstract: The present invention relates to antibodies capable of binding to human OX40 and to variants thereof comprising a modified Fc region comprising at least one mutation that enhances the Fc-Fc interaction of the antibody and at least one mutation that reduces the Fc effector functions of the antibody. The invention further provides pharmaceutical compositions comprising the antibodies and use of the antibodies for therapeutic and diagnostic procedures, in particular in cancer therapy.

Abstract: The present invention relates to the treatment of cancer, in particular breast cancer, particularly triple-negative breast cancer. More particularly, the invention concerns methods for cancer treatment involving a specific set of tumor antigens.

Abstract: The present invention provides a binding agent that binds to EpCAM and to CD137 which is useful to treat or prevent a tumor or cancer, or to prevent progression of a tumor or cancer.

Abstract: It was the object of the present invention to provide RNA with increased stability and translation efficiency and means for obtaining such RNA. It should be possible to obtain increased grades of expression by using said RNA in gene therapy approaches.

Abstract: Methods for effecting the de-differentiation of somatic cells to cells having stem cell characteristics, in particular pluripotency, include the steps of introducing RNA encoding factors inducing the de-differentiation of somatic cells into the somatic cells and culturing the somatic cells allowing the cells to de-differentiate.

Abstract: A method is proposed for identifying (“segmenting”) at least one portion of the skin of an animal which is a region of interest (e.g. a portion which is subject to an abnormality such as a tumor). The method uses at least a temperature dataset obtained by measuring the temperature of each of a plurality of points of a region of the skin. An initial segmentation may be performed using the temperature data based on a statistical model, in which each point is segmented based on its temperature and optionally that of its neighbors. The initial segmentation based on the temperature data may be improved using a three-dimensional model of the profile of the skin, and the enhanced segmentation may be used to improve the three-dimensional model.

Abstract: The invention relates to a computer-aided system for supporting teamwork by means of augmented reality (AR). According to one embodiment, the system comprises a production server, which is designed to store the three-dimensional geometry of at least part of a machine and a plurality of tasks. A spatial position in which the task should be performed and position-related information concerning the performance of the task are associated with each task. The system also comprises a plurality of user terminals, which are connected to the production server by means of a computer network, each user terminal being assigned to a person of a team. The production server is also designed to assign each person of the team a certain task, the position-related information associated with the task in question being displayed on the user terminal of the person in question.

Abstract: The present invention relates to systems and methods suitable for high-level protein production. In particular, a system comprising two separate RNA molecules is foreseen, each comprising a nucleotide sequence derived from an alphavirus: one RNA molecule comprises a RNA construct for expressing alphavirus replicase, and one RNA molecule comprises a RNA replicon that can be replicated by the replicase in trans. The system of the present invention enables expression of a protein of interest in a cell or organism, but is not associated with undesired virus-particle formation. The present invention is suitable for efficiently and safely producing a protein of interest in a target organism. Respective methods of protein production in vitro and in vivo as well as medical uses are provided herein. The present invention also provides DNA encoding the RNA molecules of the invention, and cells comprising the RNA molecules of the invention.