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 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 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 methods for predicting peptides or polypeptides such as T cell epitopes useful for immunotherapy such as for vaccination. In particular, the present invention relates to methods for predicting whether peptides or polypeptides such as tumor-associated antigens or epitopes, in particular tumor-associated neoantigens or neoepitopes, are immunogenic and, in particular, useful for immunotherapy such as 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: This disclosure relates to the field of therapeutic RNA, in particular to treat cancer. Disclosed herein are compositions, uses, and methods for reducing an unwanted response or reaction, or both, in a subject, to RNA encoding an amino acid sequence comprising a cytokine protein.

Abstract: The present invention relates to methods for predicting peptides or polypeptides such as T cell epitopes useful for immunotherapy such as for vaccination. In particular, the present invention relates to methods for predicting whether peptides or polypeptides such as tumor-associated antigens or epitopes, in particular tumor-associated neoantigens or neoepitopes, are immunogenic and, in particular, useful for immunotherapy such as 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: This disclosure relates to the field of therapeutic RNA to treat cancer, in particular advanced solid tumors such as metastatic (Stage IV) or unresectable localized cancer. Disclosed herein are compositions, uses, and methods for treatment of cancers. Administration of therapeutic RNAs to a patient having cancer disclosed herein can reduce tumor size, prolong time to progressive disease, and/or protect against metastasis and/or recurrence of the tumor and ultimately extend survival time.

Abstract: This disclosure relates to the field of therapeutic RNA to treat cancer. Disclosed herein are compositions, uses, and methods for treatment of cancers Administration of therapeutic RNAs to a patient having cancer disclosed herein can reduce tumor size, prolong time to progressive disease, and/or protect against metastasis and/or recurrence of the tumor and ultimately extend survival time.

Abstract: The present disclosure relates to methods and compositions for inducing an immune response in a subject comprising providing to the subject a peptide or protein vaccine and a binding agent, such as a bispecific antibody, binding to PD-L1 and CD137, such as human PD-L1 and human CD137, e.g., by co-administering to the subject a peptide or protein used for vaccination or a polynucleotide, in particular RNA, encoding a peptide or protein used for vaccination, and a binding agent binding to PD-L1 and CD137 or a polynucleotide, in particular RNA, encoding a binding agent binding to PD-L1 and CD137. The present disclosure further relates to medical preparations useful in the methods disclosed herein.

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 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 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 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 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 is in the field of tumor immunotherapy. In particular, the present invention provides individualized cancer vaccines specific for a patients 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 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 disclosure relates to methods and compositions for inducing an immune response in a subject comprising co-administering to the subject RNA encoding peptides or proteins used for vaccination and RNA encoding IL-2 attached to a pharmacokinetic modifying group and/or RNA encoding IL-7 attached to a pharmacokinetic modifying group. The vaccine is particularly effective if an immune checkpoint inhibitor such as an anti-PD-L1 antibody is further administered. The present disclosure further relates to methods involving the target-specific delivery of a cytokine to a target organ or target tissue.

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 methods for predicting peptides or polypeptides such as T cell epitopes useful for immunotherapy such as for vaccination. In particular, the present invention relates to methods for predicting whether peptides or polypeptides such as tumor-associated antigens or epitopes, in particular tumor-associated neoantigens or neoepitopes, are immunogenic and, in particular, useful for immunotherapy such as 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.