Abstract: The invention relates to variants of the alpha subunit of interleukin-2 receptor (IL2R) and interleukin-2 (IL2). In one embodiment, the IL2 variants described herein have amino acid substitutions at the region of IL2 that contacts the alpha (?) subunit of the heterotrimeric IL2 receptor complex, IL2R???, reducing its ability to bind and activate the heterotrimeric receptor complex. Conversely, the corresponding IL2R? variants described herein have amino acid substitutions compensating for such reduced ability of IL2 variants to bind to and activate IL2R???, preferably at amino acid residues contacted by IL2 amino acid residues that are substituted in the IL2 variants described herein.

Abstract: The present invention provides Claudin-6-specific immunoreceptors (T cell receptors and artificial T cell receptors (chimeric antigen receptors; CARs)) and T cell epitopes which are useful for immunotherapy.

Abstract: The invention relates to antibodies directed against an epitope located within the C-terminal portion of CLDN6 which are useful, for example, in diagnosing cancer and/or in determining whether cancer cells express CLDN6.

Abstract: The present invention relates to lipid particles comprising at least one cationic lipid, at least one water-soluble therapeutically effective compound and RNA. Further, the present invention relates to a pharmaceutical composition comprising such particles. Said pharmaceutical composition is useful for inducing an immune response. It is also useful in a prophylactic and/or therapeutic treatment of a disease involving an antigen. Furthermore, the present invention relates to a method for producing the particles.

Abstract: The present disclosure relates to methods and agents for enhancing the effect of immune effector cells, in particular immune effector cells that respond to interleukin-2 (IL2), for example effector T cells such as CD8+ T cells. Specifically, the present disclosure relates to methods comprising administering to a subject a polypeptide comprising IL2 or a functional variant thereof or a polynucleotide encoding a polypeptide comprising IL2 or a functional variant thereof and a polypeptide comprising type I interferon (IFN) or a functional variant thereof or a polynucleotide encoding a polypeptide comprising type I interferon or a functional variant thereof.

Abstract: The present invention relates to compositions comprising polyplex formulations for delivery of RNA to a target organ or a target cell after parenteral administration, in particular after intramuscular administration. More precisely, the present invention relates to formulations for administration of RNA such as self-replicating RNA, in particular by intramuscular injection. In more detail, the formulations comprise polyplex particles from single stranded RNA and a polyalkyleneimine. The RNA may encode a protein of interest, such as a pharmaceutically active protein. Furthermore, the present invention relates to pharmaceutical products, comprising said RNA polyplex formulations for parenteral application to humans or to animals. The present invention relates as well to manufacturing of such pharmaceutical products, comprising, optionally, steps of sterile filtration, freezing and dehydration.

Abstract: The present disclosure relates to methods and agents for enhancing the effect of T cells engineered to express chimeric antigen receptors (CARs). These methods and agents are, in particular, useful for the treatment of diseases characterized by diseased cells expressing an antigen the CAR is directed to. Specifically, the present disclosure relates to methods comprising providing to a subject T cells genetically modified to express a chimeric antigen receptor (CAR) and administering to the subject IL2 or a polynucleotide encoding IL2. The methods of the disclosure may comprise administering IL2 or a polynucleotide encoding IL2 and a further cytokine or a polynucleotide encoding a further cytokine, wherein the further cytokine may be IL7 or IL21. The T cells genetically modified to express a CAR may be provided to the subject by administering the T cells genetically modified to express a CAR or by generating the T cells genetically modified to express a CAR in the subject.

Abstract: The present invention relates to efficient methods for providing antigen-specific lymphoid cells. These lymphoid cells may be used to provide antigen specific T cell receptors having a defined MHC restriction and to identify immunologically relevant T cell epitopes. Furthermore, the present invention relates to antigen-specific T cell receptors and T cell epitopes and their use in immunotherapy.

Abstract: The present invention relates to fusion molecules of antigens, the nucleic acids coding therefor and the use of such fusion molecules and nucleic acids. In particular, said invention relates to fusion molecules, comprising an antigen and the trans-membrane region and cytoplasmic region of a MHC molecule and/or the cytoplasmic region of a MHC or a SNARE molecule.

Abstract: The present invention relates to methods for predicting T cell epitopes. In particular, the present invention relates to methods for predicting whether modifications in peptides or polypeptides such as tumor-associated neoantigens are immunogenic or not. The methods of the invention are useful, in particular, for the provision of vaccines which are specific for a patient's tumor and thus, in the context of personalized cancer vaccines.

Abstract: The invention relates to antibodies directed against an epitope located within the C-terminal portion of CLDN6 which are useful, for example, in diagnosing cancer and/or in determining whether cancer cells express CLDN6.

Abstract: The present invention relates to methods for predicting T cell epitopes useful for vaccination. In particular, the present invention relates to methods for predicting whether modifications in peptides or polypeptides such as tumor-associated neoantigens are immunogenic and, in particular, useful for vaccination, or for predicting which of such modifications are most immunogenic and, in particular, most useful for vaccination. The methods of the invention may be used, in particular, for the provision of vaccines which are specific for a patient's tumor and thus, in the context of personalized cancer vaccines.

Abstract: The present invention relates to local delivery to an organ and/or tissue of an agent such as a peptide and/or polypeptide, by administration of an RNA molecule encoding such agent to an afferent blood vessel of the organ and/or tissue. The agent is thus able to provide its biological function, e.g., therapeutic effect, locally and avoid unwanted systemic effects, including any toxicity observed when the agent encoded by the RNA and/or the encoding RNA itself is administered systemically.

Abstract: Multispecific antibodies binding to human CD40 and human CD137, methods for preparing such multispecific antibodies, and methods of using such multispecific antibodies for therapeutic or other purposes.

Abstract: The present invention relates to the provision of vaccines which are specific for a patient's tumor and are potentially useful for immunotherapy of the primary tumor as well as tumor metastases. In one aspect, the present invention relates to a method for providing an individualized cancer vaccine comprising the steps: (a) identifying cancer specific somatic mutations in a tumor specimen of a cancer patient to provide a cancer mutation signature of the patient; and (b) providing a vaccine featuring the cancer mutation signature obtained in step (a). In a further aspect, the present invention relates to vaccines which are obtainable by said method.

Abstract: This disclosure relates to the field of therapeutic RNAs for treatment of subjects that have failed, or become intolerant, resistant, or refractory to an anti-programmed cell death 1 (PD-1) or anti-programmed cell death 1 ligand 1 (PD-L1) therapy, including innate and acquired PD-1 and/or PD-L1 therapy, as well as in subjects with advanced-stage, unresectable, or metastatic solid tumor cancers with or without failure, intolerance, resistance, or refraction to an anti-programmed cell death 1 (PD-1) or anti-programmed cell death 1 ligand 1 (PD-L1) therapy.

Abstract: The present invention embraces a RNA replicon that can be replicated by a replicase of alphavirus origin. The RNA replicon comprises sequence elements required for replication by the replicase, but these sequence elements do not encode any protein or fragment thereof, such as an alphavirus non-structural protein or fragment thereof. Thus, in the RNA replicon according to the invention, sequence elements required for replication by the replicase and protein-coding region(s) are uncoupled. According to the present invention the uncoupling is achieved by the removal of at least one initiation codon compared to a native alphavirus genomic RNA. In particular, the RNA replicon comprises a 5? replication recognition sequence, wherein the 5? replication recognition sequence is characterized in that it comprises the removal of at least one initiation codon compared to a native alphavirus 5? replication recognition sequence.

Abstract: The present invention generally embraces the treatment of diseases by targeting cells expressing an antigen on the cell surface. In particular the invention relates to recombinant antigen receptors and uses thereof. T cells engineered to express such antigen receptors are useful in the treatment of diseases characterized by expression of one or more antigens bound by the antigen receptors.

Abstract: Multispecific antibodies binding to human CD40 and human CD137, methods for preparing such multispecific antibodies, and methods of using such multispecific antibodies for therapeutic or other purposes.

Abstract: The present invention relates to methods for predicting T cell epitopes. In particular, the present invention relates to methods for predicting whether modifications in peptides or polypeptides such as tumor-associated neoantigens are immunogenic or not. The methods of the invention are useful, in particular, for the provision of vaccines which are specific for a patient's tumor and, thus, in the context of personalized cancer vaccines.