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.