The present invention is directed to a pharmaceutical composition including (e.g. for use as an adjuvant) a polymeric carrier cargo complex, comprising as a carrier a polymeric carrier formed by disulfide-crosslinked cationic components; and as a cargo at least one nucleic acid molecule, and at least one antigen that is selected from an antigen from a pathogen associated with infectious disease; an antigen associated with allergy or allergic disease; an antigen associated with autoimmune disease; or an antigen associated with a cancer or tumour disease, or in each case a fragment, variant and/or derivative of said antigen. The pharmaceutical composition allows for efficient induction of an adaptive immune response directed against said antigen. The present invention furthermore provides kits, as well as the use of the pharmaceutical composition or the kit as a vaccine, particularly in the treatment of infectious diseases, allergies, autoimmune diseases and tumour or cancer diseases.

The present application provides peripheral blood mononuclear cells comprising an antigen, methods of manufacturing such PBMCs, and methods of using such PBMCs, such as for modulating an immune response in an individual. In some embodiments, the PBMCs are conditioned by incubating the PBMC in the presence of an adjuvant.

The present invention provides a vaccine for preventing and/or treating infections with human papillomavirus. The present invention relates to a lipid particle encapsulating a nucleic acid molecule capable of expressing the E6 and E7 antigens of human papillomavirus, wherein the lipid comprises a cationic lipid represented by general formula (Ia) or a pharmaceutically acceptable salt thereof:

##STR00001##

wherein R.sup.1 and R.sup.2 each independently represent a C.sub.1-C.sub.3 alkyl group;
L.sup.1 represents a C.sub.17-C.sub.19 alkenyl group which may have one or a plurality of C.sub.2-C.sub.4 alkanoyloxy groups;
L.sup.2 represents a C.sub.10-C.sub.19 alkyl group which may have one or a plurality of C.sub.2-C.sub.4 alkanoyloxy groups or a C.sub.10-C.sub.19 alkenyl group which may have one or a plurality of C.sub.2-C.sub.4 alkanoyloxy groups; and
p is 3 or 4.

Embodiments of the present disclosure pertain generally to head and neck squamous cell carcinomas (HNSCCs) related to human papillomavirus subtype 16 (HPV16) infections. More particularly, the present disclosure provides novel immunogenic epitopes from HPV16 E2, E6 and E7 antigens restricted by common human leukocyte antigen (HLA) alleles for the diagnosis and treatment of HNSCC. The HPV16 epitopes identified in the present disclosure can be used in combination with blockade of HPV16+ HNSCC-specific checkpoints for targeted immunotherapy.

The present invention relates to a multivalent HPV immunogenic composition for preventing human papillomavirus (HPV) related diseases or infections and uses thereof. Said multivalent HPV immunogenic composition comprises: HPV virus-like particles assembled from L1 proteins of HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and one or more HPV virus-like particles assembled from L1 proteins of other pathogenic HPV types. In one embodiment, said one or more other pathogenic HPV types are selected from HPV Types 35, 39, 51, 56 and 59. In one embodiment, at least one of said HPV virus-like particles is a chimeric HPV virus-like particle, and said chimeric HPV virus-like particle comprises one or more chimeric HPV L1 proteins.

Embodiments of the disclosure concern methods and compositions for immunotherapy for human papillomavirus infection and diseases associated therewith. In specific embodiments, methods concern production of immune cells that target one or more antigens of HPV16 and/or HPV18, including methods with stimulation steps that employ IL-7 and IL-15, but not IL-6 and/or IL-12. Other specific embodiments utilize stimulations in the presence of certain cells, such as costimulatory cells and certain antigen presenting cells.

The present disclosure relates to IL2 agonists with improved therapeutic profiles.

The present invention relates to the field of mRNA formulations, and in particular provides a combination of one or more mRNA molecules encoding the functional immunostimulatory proteins CD40L, CD70 and caTLR4; and one or more mRNA molecules encoding an antigen. The combinations of the present invention are in particular characterized in that the mRNA molecules comprise a 5′ CAP-1 structure and may further contain one or more modified nucleosides, such as pseudouridines. The present invention also provides compositions comprising said combinations and uses thereof, in particular in vaccination, and treatment of cell proliferative disorders.

Methods and compositions for altering the microenvironment of a tumor are provided. The methods comprise reducing the population of tumor-residing immune suppressive regulatory T-cells, increasing the population of tumor lysing T-cells (such as CD8+ T-cells) and improving the efficacy of cancer immunotherapy. The compositions comprise the use of cationic lipids optionally combined with autologous antigens, non-autologous antigens, or tumor-associated antigens.

The invention covers the use of certain classes of lipids including cationic lipids in ex-vivo dendritic cell therapies. The cationic lipids enhance antigen uptake, processing and presentation of the processed antigens by dendritic cells to CD8+ and CD4+ T-cells via the MHC classes I and II presentation pathways respectively. Antigen uptake via cationic lipid by dendritic cells result in significant lowering of the population of the immune suppressive regulatory T cells in the tumors and a significant increase of the tumor targeting cytotoxic T-cells. Loss of regulatory T cells and increase of tumor specific cytotoxic cells are conducive to effective elimination of the tumors.