Abstract: The present invention relates to non-immunogenic RNA. This RNA forms the basis for the development of therapeutic agents for inducing tolerance towards an autoantigen and thus, for the treatment of autoimmune diseases.

Abstract: The present invention is in the field of immunotherapy, in particular tumor immunotherapy. The present invention provides pharmaceutical formulations for delivering RNA to antigen presenting cells such as dendrite cells (DCs) in the spleen after systemic administration. In particular, the formulations described herein enable to induce an immune response after systemic administration of antigen-coding RNA.

Abstract: The present invention relates to non-immunogenic RNA. This RNA forms the basis for the development of therapeutic agents for inducing tolerance towards an autoantigen and thus, for the treatment of autoimmune diseases.

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: The present invention relates to RNA decorated particles such as RNA decorated lipid particles, preferably to RNA decorated liposomes. Further, the present invention relates to a pharmaceutical composition comprising RNA decorated particles such as RNA decorated lipid particles, preferably RNA decorated liposomes. 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 RNA decorated particles such as RNA decorated lipid particles, preferably RNA decorated liposomes.

Abstract: The present disclosure relates to methods and agents for antigen vaccination and inducing effective antigen-specific immune effector cell responses such as T cell responses. Specifically, the present disclosure relates to methods comprising administering to a subject (i) non-immunogenic RNA encoding a peptide or protein comprising an epitope for inducing an immune response against an antigen in the subject, i.e., non-immunogenic RNA encoding vaccine antigen; and (ii) an immunostimulant or RNA encoding an immunostimulant. Administering to the subject non-immunogenic RNA encoding vaccine antigen may provide (following expression of the RNA by appropriate target cells) vaccine antigen for stimulation, priming and/or expansion of immune effector cells and, thus, may induce an immune response against vaccine antigen (and disease-associated antigen) in the subject.

Abstract: The present invention is in the field of immunotherapy, in particular tumor immunotherapy. The present invention provides pharmaceutical formulations for delivering RNA to antigen presenting cells such as dendrite cells (DCs) in the spleen after systemic administration. In particular, the formulations described herein enable to induce an immune response after systemic administration of antigen-coding RNA.

Abstract: Tumor cells often evade an immune response, e.g., by reducing or eliminating MHC expression and/or IFN-signaling, which enables uncontrolled growth. We demonstrate herein that antibody-based immunotherapy in combination with IL2 administration is an effective therapy against such resistant tumors. Specifically, the present disclosure relates to methods of treating a subject with cancer that is at least partially resistant to an MHC-dependent T cell response comprising administering to the subject: a. a polypeptide comprising IL2 or a functional variant thereof or a polynucleotide encoding a polypeptide comprising IL2 or a functional variant thereof; and b. antibody-based immunotherapy.

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 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: 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 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 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 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 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 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: 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 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.