Immunotherapy against neuronal and brain tumors

Abstract

The present invention is inter alia directed to an artificial nucleic acid that encodes at least one polypeptide or protein that comprises at least one antigenic peptide or protein from each of the tumour-associated antigens Brevican core protein (BCAN), Neuroligin-4, X-linked (NLGNX4), Receptor-type tyrosine protein phosphatase zeta (PTPRZ1) and Baculoviral IAP repeat-containing protein (BIRC5) or a variant of each of these. Further provided is a set of artificial nucleic acids, wherein the set encodes said combination of antigenic peptides or proteins. Moreover, the invention provides a composition comprising the artificial nucleic acid or set. The invention also provides a combination and a kit or kit of parts. Also provided are first, second, and further medical uses of the herein specified subject matter, preferably the use as a medicament in the treatment or prevention of a tumour or cancer disease, preferably in the treatment or prevention of glioblastoma or astrocytoma.

Description

Immunotherapy against neuronal and brain tumorsBackground of the InventionThe present invention relates to the field of cancer immunotherapy.Cancer is a major global health problem and is one of the leading causes of death worldwide. Traditional cancer treatments, such as surgery, chemotherapy, and radiation therapy, have limited efficacy and can cause significant side effects. Immunotherapy, which involves harnessing the power of the immune system to target cancer cells, has emerged as a promising new approach for the treatment of cancer. Cancer immunotherapy exploits the fact that cancer cells often present molecules on their surface that can be detected by the immune system, known as tumour antigens, which are often proteins or other macromolecules. However, identifying tumour antigen combinations that are suitable for immunotherapy of cancer remains an ongoing challenge.In recent years, nucleic acid, such as RNA, has emerged as a promising therapeutic tool for the treatment of various diseases, as it can be used to direct the production of proteins that can inhibit or reduce the growth or survival of cancer cells. The advantages of using RNA include transient expression and its nontransforming character - RNA does not need to enter the nucleus in order to be expressed and moreover cannot integrate into the host genome, thereby eliminating the risk of oncogenesis. Accordingly, nucleic acid, such as RNA, may represent a promising class of molecules for use in immunotherapy of tumour diseases.Neuronal and brain tumours such glioblastomas (GBM) or astrocytoma belong to the tumour types with the highest lethal rates. Most tumour cells of GBM or astrocytoma are the most undifferentiated ones among brain tumours. GBM cells have high potential of migration and proliferation and are highly invasive, leading to very poor prognosis. GBM lead to death due to rapid, aggressive, and infiltrative growth in the brain. GBM or astrocytoma are relatively resistant to radiation and chemotherapy, and, therefore, post-treatment recurrence rates are high. In addition, the immune response to the neoplastic cells is rather ineffective in completely eradicating all neoplastic cells following resection and radiation therapy. Accordingly, there is an urgent need for an immunotherapy against neuronal and brain tumours such as GBM or astrocytomas.The object of the present invention is to provide novel compounds, which are suitable for use in cancer immunotherapy, in particular in the treatment or prevention of glioblastoma or astrocytoma.The object as defined above is solved by the subject-matter of the present invention as defined herein. In particular, the inventors surprisingly found that an artificial nucleic acid, preferably an mRNA, encoding thespecific combination of antigenic peptides or proteins is effective in the treatment or prevention of a tumour or cancer disease, in particular in the treatment or prevention of glioblastoma or astrocytoma.Short Description of the InventionThe present invention provides a novel artificial nucleic acid, which is suitable for use in cancer immunotherapy. More specifically, the invention concerns an artificial nucleic acid comprising at least one coding sequence, wherein the at least one coding sequence encodes at least one polypeptide or protein, the at least one polypeptide or protein comprising at least one antigenic peptide or protein from each of the tumour-associated antigens Brevican core protein (BCAN), Neuroligin-4, X-linked (NLGNX4), Receptortype tyrosine-protein phosphatase zeta (PTPRZ1) and Baculoviral IAP repeat-containing protein 5 (BIRC5) or a variant of each of these. The invention further relates to a set of artificial nucleic acids, wherein at least two artificial nucleic acids together encode said combination of antigenic peptides or proteins. Moreover, the invention provides a composition, preferably a pharmaceutical composition, comprising the artificial nucleic acid or the artificial nucleic acid set. In addition, the invention is directed to a combination of pharmaceutical compositions, wherein each of the pharmaceutical compositions comprises at least one artificial nucleic acid and wherein the artificial nucleic acids of the pharmaceutical compositions of the combination together encode the combination of antigenic peptides or proteins. Furthermore, the invention provides a kit or kit of parts comprising the artificial nucleic acid, the artificial nucleic acid set, the (pharmaceutical) composition or the combination of (pharmaceutical) compositions as described herein. Also provided herein is the artificial nucleic acid, the artificial nucleic acid set, the (pharmaceutical) composition or the combination of (pharmaceutical) compositions as described herein for use as a medicament, preferably in the treatment or prevention of a tumor or cancer disease, more preferably in the treatment or prevention of glioblastoma or astrocytoma.DefinitionsFor the sake of clarity and readability the following definitions are provided. Any technical feature mentioned for these definitions may be read on each and every embodiment of the invention. Additional definitions and explanations may be specifically provided in the context of the embodiments described herein.Percentages in the context of numbers should be understood as relative to the total number of the respective items. In other cases, and unless the context dictates otherwise, percentages should be understood as percentages by weight (wt.-%).About: The term “about” is used when determinants or values do not need to be identical, i.e. 100% the same. Accordingly, “about” means, that a determinant or value may diverge by 1 % to 20%, preferably by 1 % to 10%. Preferably, “about” means, that a determinant or value may diverge by + / -1 %, + / -2%, + / -3%, + / -4%, + / -5%, + / -6%, + / -7%, + / -8%, + / -9%, + / -10%.Cationic: The term “cationic” means that the respective structure bears a positive charge, either permanently or not permanently, for example in response to certain conditions such as pH. Thus, the term “cationic” covers both “permanently cationic” and “cationisable”. The term “permanently cationic” means,e.g., that the respective compound, or group, or atom, is positively charged at any pH value or hydrogen ion activity of its environment. Typically, the positive charge results from the presence of a quaternary nitrogen atom.The term “cationisable” as used herein means that a compound or group or atom, is positively charged at a lower pH and uncharged at a higher pH of its environment. Also in non-aqueous environments where no pH value can be determined, a cationisable compound, group or atom is positively charged at a high hydrogen ion concentration and uncharged at a low concentration or activity of hydrogen ions. It depends on the individual properties of the cationisable or polycationisable compound, in particular the pKa of the respective cationisable group or atom, at which pH or hydrogen ion concentration it is charged or uncharged. In diluted aqueous environments, the fraction of cationisable compounds, groups or atoms bearing a positive charge may be estimated using the so-called Henderson-Hasselbalch equation which is well-known to a person skilled in the art. E.g., in some embodiments, if a compound or moiety is cationisable, it is preferred that it is positively charged at a pH value of about 1 to 9, preferably 4 to 9, 5 to 8 or even 6 to 8, more preferably of a pH value of or below 9, of or below 8, of or below 7, most preferably at physiological pH values, e.g. about 7.3 to 7.4, i.e. under physiological conditions, particularly under physiological salt conditions. In other embodiments, it is preferred that the cationisable compound or moiety is predominantly neutral at physiological pH values, e.g. about 7.0-7.4, but becomes positively charged at lower pH values. In some embodiments, the preferred range of pKa for the cationisable compound or moiety is about 5 to about 7.cds The terms “coding sequence” or “coding region” and the corresponding abbreviation “cds” as used herein is intended to refer to a sequence of several nucleotide triplets, which may be translated into a peptide or protein. A coding sequence in the context of the present invention may be a DNA or RNA sequence consisting of a number of nucleotides that may be divided by three, which typically starts with a start codon and which preferably terminates with a stop codon. Suitably in the context of the invention, the coding sequence encodes at least one tumour antigen, accordingly, the coding sequence provides the information that is translated into least one tumour antigen as defined herein.Derived from: The term “derived from” as used herein in the context of a nucleic acid e. for a nucleic acid“derived from” (another) nucleic acid, means that the nucleic acid, which is derived from (another) nucleic acid, shares e.g. at least 60%, 70%, 80%, 81 %, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity or are identical with the nucleic acid from which it is derived. The skilled person is aware that sequence identity is typically calculated for the same types of nucleic acids, i.e. for DNA sequences or for RNA sequences. Thus, it is understood, if a DNA is “derived from” an RNA or if an RNA is “derived from” a DNA, in a first step the RNA sequence is converted into the corresponding DNA sequence (in particular by replacing the uracils (U) by thymidines (T) throughout the sequence) or, vice versa, the DNA sequence is converted into the corresponding RNA sequence (in particular by replacing the T by U throughout the sequence). Thereafter, the sequence identity of the DNA sequences or the sequence identity of the RNA sequences is determined. Preferably, a nucleic acid “derived from” a nucleic acid also refers to nucleic acid, which is modified in comparison to the nucleicacid from which it is derived, e.g. in order to increase RNA stability even further and / or to prolong and / or increase protein production. In the context of amino acid sequences the term “derived from” means that the amino acid sequence, which is derived from (another) amino acid sequence, shares e.g. at least 60%, 70%, 75%, 80%, 81 %, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity or are identical with the amino acid sequence from which it is derived.: The term “epitope as used herein will be recognized and understood by the person of ordinary skill in the art, and is e.g. intended to refer to T cell epitopes and B cell epitopes. T cell epitopes are typically parts of the antigenic peptides or proteins, such as the at least one antigenic peptide or protein encoded by the artificial nucleic acid described herein, and may comprise fragments of said antigenic peptide or protein, preferably having a length of about 6 to about 20 or even more amino acids, e.g. fragments as processed and presented by MHC class I molecules, preferably having a length of about 8 to about 11 amino acids, e.g. 8, 9, 10, or 11 (or even 12 amino acids), or fragments as processed and presented by MHC class II molecules, preferably having a length of about 13 to about 20 or even more amino acids. These fragments are typically recognized by T cells in form of a complex consisting of the peptide fragment and an MHC molecule, i.e. the fragments are typically not recognized in their native form. As used herein, the term “T-cell epitope” also refers to a predicted T-cell epitope, e.g. a T-cell epitope as predicted by an algorithm. Suitable algorithms are known in the art and include software (for example, NetMHCpan 4.1), which may be used for MHC-I binding predictions. B cell epitopes are typically fragments located on the outer surface of (native) protein or peptide antigens, preferably having 5 to 15 amino acids, more preferably having 5 to 12 amino acids, even more preferably having 6 to 9 amino acids, which may be recognized by antibodies, i.e. in their native form. Such epitopes of proteins or peptides may furthermore be selected from any of the herein mentioned variants of such proteins or peptides. In this context epitopes can be conformational or discontinuous epitopes which are composed of segments of the proteins or peptides as defined herein that are discontinuous in the amino acid sequence of the proteins or peptides as defined herein but are brought together in the three-dimensional structure or continuous or linear epitopes which are composed of a single polypeptide chain.The term “T-cell epitope” refers to a part or fragment of a protein or antigen that is recognized by a T cell when presented in the context of major histocompatibility complex (MHC) molecules, including MHC class I and MHC class II molecules and relating to a complex of genes which is present in all vertebrates. MHC proteins or molecules are important for signalling between lymphocytes and antigen presenting cells or diseased cells in immune reactions, wherein the MHC proteins or molecules bind peptide epitopes and present them for recognition by T-cell receptors on T cells. The proteins encoded by the MHC are expressed on the surface of cells, and display both self-antigens (peptide fragments from the cell itself) and non-self- antigens (e.g., fragments of invading microorganisms) to a T cell. In the case of class I MHC / peptide complexes, the binding peptides (MHC class I ligands) are typically about 8 to about 11 amino acids long although longer or shorter peptides may be effective. In the case of class II MHC / peptide complexes, the binding peptides (MHC class II ligands) are typically about 10 to about 25 amino acids long and are in particular about 13 to about 18 amino acids long, whereas also longer and shorter peptides may be effective.The term “fragment” as used herein in the context of a nucleic acid sequence (e.g. RNA or aDNA) or an amino acid sequence may typically be a shorter portion of a full-length sequence of e.g. a nucleic acid sequence or an amino acid sequence. Accordingly, a fragment typically consists of a sequence that is identical to the corresponding stretch within the full-length sequence. A preferred fragment of a sequence in the context of the present invention, consists of a continuous stretch of entities, such as nucleotides or amino acids corresponding to a continuous stretch of entities in the molecule the fragment is derived from, which represents at least 50% , 60%, 70%, 80%, or 90% of the total full-length molecule from which the fragment is derived. The term “fragment” as used throughout the specification in the context of proteins or peptides may, typically, comprise a sequence of a protein or peptide as defined herein, which is, with regard to its amino acid sequence, N-terminally and / or C-terminally truncated compared to the amino acid sequence of the original protein. The term “fragment” as used throughout the specification in the context of RNA sequences may, typically, comprise an RNA sequence that is 5’-terminally and / or 3’- terminally truncated compared to the reference RNA sequence. Such truncation may thus occur either on the amino acid level or correspondingly on the nucleic acid level. A sequence identity with respect to such a fragment as defined herein may therefore preferably refer to the entire protein or peptide as defined herein or to the entire (coding) nucleic acid molecule of such a protein or peptide.The term “identity” as used herein in the context of a nucleic acid sequence or an amino acid sequence will be recognized and understood by the person of ordinary skill in the art, and is e.g. intended to refer to the percentage to which two sequences are identical. To determine the percentage to which two sequences are identical, e.g. nucleic acid sequences or amino acid (aa) sequences, preferably the aa sequences encoded by the nucleic acid sequence as defined herein or the aa sequences themselves, the sequences can be aligned in order to be subsequently compared to one another. Therefore, e.g. a position of a first sequence may be compared with the corresponding position of the second sequence. If a position in the first sequence is occupied by the same residue as is the case at a position in the second sequence, the two sequences are identical at this position. If this is not the case, the sequences differ at this position. If insertions occur in the second sequence in comparison to the first sequence, gaps can be inserted into the first sequence to allow a further alignment. If deletions occur in the second sequence in comparison to the first sequence, gaps can be inserted into the second sequence to allow a further alignment. The percentage to which two sequences are identical is then a function of the number of identical positions divided by the total number of positions including those positions which are only occupied in one sequence. The percentage to which two sequences are identical can be determined using an algorithm, e.g. an algorithm integrated in the BLAST program.ic: The terms “immunogen or “immunogenic” will be recognized and understood by the person of ordinary skill in the art, and are e.g. intended to refer to a compound that is able to stimulate / induce an immune response. Preferably, an immunogen is a peptide, polypeptide, or protein.Nucleic acid nucleic acid molecule The terms “nucleic acid” or “nucleic acid molecule” will be recognized and understood by the person of ordinary skill in the art. The term “nucleic acid” or “nucleic acid molecule”as used herein preferably refers to DNA (molecules) or RNA (molecules). It is preferably used synonymously with the term polynucleotide. Preferably, a nucleic acid or a nucleic acid molecule is a polymer comprising or consisting of nucleotide monomers, which are covalently linked to each other by phosphodiester-bonds of a sugar / phosphate-backbone. The term “nucleic acid molecule” also encompasses modified nucleic acid molecules, such as base-modified, sugar-modified, or backbone- modified DNA or RNA molecules as defined herein.Nucleic acid: The terms “nucleic acid sequence”, “DNA sequence”, “RNA sequence” will be recognized and understood by the person of ordinary skill in the art, and e.g. refer to a particular and individual order of the succession of its nucleotides.In the context of the invention, the term “nucleic acid species” is not restricted to mean one single molecule but is understood to comprise an ensemble of essentially identical nucleic acid molecules. Accordingly, it may relate to a plurality of essentially identical nucleic acid molecules. In the context of the invention the term “RNA species” is not restricted to mean one single molecule but is understood to comprise an ensemble of essentially identical RNA molecules. Accordingly, it may relate to a plurality of essentially identical RNA molecules.RNA: The term “RNA” is the usual abbreviation for ribonucleic acid It is a nucleic acid molecule, i.e. a polymer consisting of nucleotide monomers. These nucleotides are usually adenosine-monophosphate (AMP), uridine-monophosphate (UMP), guanosine-monophosphate (GMP) and cytidine-monophosphate (CMP) monomers or analogues thereof, which are connected to each other along a so-called backbone. The backbone is typically formed by phosphodiester bonds between the sugar, i.e. ribose, of a first and a phosphate moiety of a second, adjacent monomer. The specific order of the monomers, i.e. the order of the bases linked to the sugar / phosphate-backbone, is called the RNA sequence. RNA can be obtained by transcription of a DNA sequence, e.g., inside a cell or in vitro. In the context of the invention, the RNA may be obtained by RNA in vitro transcription. Alternatively, RNA may be obtained by chemical synthesis.ion: The terms “RNA in vitro transcription” or “in vitro transcription” relate to a process wherein RNA is synthesized in a cell-free system in vitro. RNA may be obtained by DNA-dependent in vitro transcription of an appropriate DNA template, which is typically a linear DNA template (e.g. linearized plasmid DNA or PCR product). The promoter for controlling RNA in vitro transcription can be any promoter for any DNA-dependent RNA polymerase. Particular examples of DNA-dependent RNA polymerases are the T7, T3, SP6, or Syn5 RNA polymerases. In the context of the invention, the DNA template is typically linearized with a suitable restriction enzyme before it is subjected to RNA in vitro transcription. Reagents typically used in RNA in vitro transcription include: a DNA template (linearized plasmid DNA or PCR product) with a promoter sequence that has a high binding affinity for its respective RNA polymerase such as bacteriophage-encoded RNA polymerases (T7, T3, SP6, or Syn5); ribonucleotide triphosphates (NTPs) for the four bases (adenine, cytosine, guanine and uracil); optionally, a cap analogue as defined herein; optionally, modified nucleotides as defined herein; a DNA-dependent RNA polymerase capable of bindingto the promoter sequence within the DNA template (e.g. T7, T3, SP6, or Syn5 RNA polymerase); optionally, a ribonuclease (RNase) inhibitor to inactivate any potentially contaminating RNase; optionally, pyrophosphatase; MgCh; a buffer (TRIS or HEPES) to maintain a suitable pH value, which can also contain antioxidants (e.g. DTT), and / or polyamines such as spermidine.The term “tumour-associated antigen” (“TAA”) as used herein typically refers to antigens that are expressed by both normal and neoplastic tissue. TAAs may also be defined as self-proteins that are abnormally expressed by cancer cells. TAAs can be loosely categorized as oncofoetal (typically only expressed in foetal tissues and in cancerous somatic cells), overexpressed / accumulated (typically highly overexpressed in neoplastic tissue compared to normal tissue), cancer-testis / cancer- germline antigens (expressed only by cancer cells and adult reproductive tissues such as testis and placenta), differentiation antigens / lineage-restricted (typically derived from proteins that are expressed in a given type of tumour and the corresponding healthy tissue and expressed largely by a single cancer histotype), post translationally altered (tumour-associated alterations in glycosylation, etc.), or idiotypic (highly polymorphic genes where a tumour cell expresses a specific “clonotype”, i.e., as in B cell, T cell lymphoma / leukaemia resulting from clonal aberrancies). By some authors also oncoviral antigens (encoded by tumorigenic transforming viruses) are considered TAAs. It should be stressed that these categories are not mutually exclusive and TAAs may fall into more than one category.The term “variant” as used herein in the context of a nucleic acid sequence will be recognized and understood by the person of ordinary skill in the art, and is e.g. intended to refer to a variant of a nucleic acid sequence derived from another nucleic acid sequence. E.g., a variant of a nucleic acid sequence may exhibit one or more nucleotide deletions, insertions, additions and / or substitutions compared to the nucleic acid sequence from which the variant is derived. A variant of a nucleic acid sequence may at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the nucleic acid sequence the variant is derived from. A variant may be a functional variant in the sense that the variant has retained at least 50%, 60%, 70%, 80%, 90%, or 95% or more of the function of the sequence where it is derived from. A “variant” of a nucleic acid sequence may have at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% nucleotide identity over a stretch of at least 30, 50, 75 or 100 nucleotide of such nucleic acid sequence.The term “variant” as used herein in the context of proteins or peptides is e.g. intended to refer to a proteins or peptide variant having an amino acid sequence which differs from the original sequence in one or more mutation(s) / substitution(s), such as one or more substituted, inserted and / or deleted amino acid(s). A variant of an amino acid sequence may be at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence the variant is derived from. Preferably, these fragments and / or variants have the same, or a comparable specific property. Insertions and substitutions are possible, in particular, at those sequence positions which cause no modification to the three-dimensional structure or do not affect the binding region. Modifications to a three- dimensional structure by insertions) or deletion(s) can easily be determined e.g. using CD spectra (circular dichroism spectra). A variant of a protein may be a functional variant of the protein, which means that thevariant exerts essentially the same, or at least 40%, 50%, 60%, 70%, 80%, 90% of the function of the protein it is derived from. A “variant” of a protein or peptide may have at least 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% amino acid identity over a stretch of at least 10, 15, 30, 50, 75 or 100 amino acids of such protein or peptide.Where reference is made to “SEQ ID NOs” of other patent applications or patents, said sequences, e.g. amino acid sequences or nucleic acid sequences, are explicitly incorporated herein by reference. For “SEQ ID NOs” provided herein, information provided under “feature key”, i.e. “source” (for nucleic acids or proteins) or “misc_feature” (for nucleic acids) or “REGION” (for proteins), in the sequence listing according to WIPO ST.26 Standard is also explicitly included herein in its entirety. Where reference is made to “SEQ ID NOs” in the context of RNA sequences, the skilled person will be able to derive RNA sequences from the referenced SEQ ID NOs also in cases where DNA sequences are provided. Where reference is made to “SEQ ID NOs” in the context of DNA sequences, the skilled person will be able to derive respective DNA sequences from the referenced SEQ ID NOs also in cases where RNA sequences are provided.Detailed Description of the Invention1 : Artificial nucleic acid:In a first aspect, the present invention provides an artificial nucleic acid comprising at least one coding sequence, wherein the at least one coding sequence encodes at least one polypeptide or protein, the at least one polypeptide or protein comprising at least one antigenic peptide or protein from at least one of the tumour-associated antigens (TAA)- Brevican core protein (BCAN) or a variant thereof,- Neuroligin-4, X-linked (NLGNX4) or a variant thereof,- Receptor-type tyrosine-protein phosphatase zeta (PTPRZ1) or a variant thereof, and- Baculoviral IAP repeat-containing protein 5 (BIRC5) or a variant thereof.The inventors unexpectedly found that antigenic peptides or proteins derived from a specific combination of TAAs are effective in inducing an immune response against cancer as further outlined herein.In some embodiments, the artificial nucleic acid of the invention encodes at least one polypeptide or protein that comprises at least one (e.g. 1 , 2, 3, 4 or more) antigenic peptide(s) or protein(s) from a combination of tumour-associated antigens (TAA), wherein the combination of TAAs comprises at least one, two, or three from the list comprising BCAN, NLGN4X, PTPRZ1 , and BIRC5.Brevican core protein (BCAN; Uniprot PGCB_HUMAN): BCAN is a brain-specific member of the lectican family of chondroitin sulphate proteoglycans. Two BCAN isoforms have been reported: a full-length isoform that is secreted into the extracellular matrix and a shorter isoform with a sequence that predicts a glycophosphatidylinositol (GPI) anchor.Neuroligin 4, X-linked (NLGN4X; Uniprot NLGNX_HUMAN): Neuroligin 4, X-linked is a member of a cell adhesion protein family that appears to play a role in the maturation and function of neuronal synapses. An upregulation of NLGN4X has been described from human embryonic neural stem cells and adult human olfactory bulb-derived neural stem cells.Receptor-type tyrosine-protein phosphatase zeta (PTPRZ1 ; Uniprot PTPRZ_HUMAN): PTPRZ1 is a member of the receptor type protein tyrosine phosphatase family and encodes a single-pass type I membrane protein with two cytoplasmic tyrosine-protein phosphatase domains, an alpha-carbonic anhydrase domain and a fibronectin type-ill domain. PTPRZ1 is expressed primarily in the nervous system and is synthesized by glial progenitors, and astrocytes.Baculoviral IAP repeat-containing protein 5 (BIRC5; survivin; Uniprot BIRC5_HUMAN): BIRC5 (survivin) is a member of the inhibitor of apoptosis protein (IAP) family. Survivin is overexpressed in a multitude of cancer entities. In general, overexpression of survivin is thought to be associated with shorter overallsurvival and higher malignancy grades.Due to the lack of commonly used abbreviations for the proteins of these TAA, the respective abbreviations for the gene names of these TAAs (i.e. BCAN, NLGN4X, PTPRZ1 and BIRC5) are used throughout the present invention for better readability, e.g. also in cases where passages refer to the respective polypeptide or protein encoded by the gene.The specific features and embodiments that are described in the context of the first aspect, that is the artificial nucleic acid of the invention, are likewise applicable to any other aspect of the invention, such as the artificial nucleic acid set, the (pharmaceutical) composition and the combination of pharmaceutical compositions as described herein.The term “artificial nucleic acid” refers to a nucleic acid that does not occur naturally. In other words, an artificial nucleic acid may be understood as a non-natural nucleic acid molecule. Such nucleic acid molecules may be non-natural due to their individual sequence (e.g. G / C content modified coding sequence, UTRs) and / or due to other modifications, e.g. structural modifications of nucleotides. As used herein, an artificial nucleic acid molecule may preferably comprise at least one heterologous element, such as a heterologous nucleic acid sequence. A heterologous nucleic acid sequence is typically a nucleic acid sequence that does not naturally occur in the same molecule as other nucleic acid sequence elements present in the artificial nucleic acid. Moreover, a heterologous nucleic acid sequence is not from the same gene or the same genomic fusion or the same naturally occurring transcript. Typically, artificial nucleic acid may be designed and / or generated by genetic engineering to correspond to a desired artificial sequence of nucleotides. In this context, an artificial nucleic acid is a sequence that may not occur naturally, i.e. a sequence that differs from the wild type sequence / the naturally occurring sequence by at least one nucleotide. The term “artificial nucleic acid” is not restricted to mean “one single molecule” but is understood to comprise an ensemble of essentially identical nucleic acid molecules. The term “artificial nucleic acid” as used herein may relate to artificial DNA or, preferably, to artificial RNA. Preferably, the artificial nucleic isselected from an artificial DNA or an artificial RNA. In particularly preferred embodiments, the artificial nucleic acid is an mRNA.The at least one coding sequence of the artificial nucleic acid described herein encodes at least one polypeptide or protein, wherein the at least one polypeptide or protein comprises at least one antigenic peptide or protein from at least one tumor-associated antigen (TAA), preferably a TAA as defined herein, more preferably at least one antigenic peptide or protein from BCAN, NLGN4X, PTPRZ1 and / or BIRC5.The term “antigenic protein” or “immunogenic protein” as used herein are preferably used in the context of a full-length antigen, e.g. a full-length TAA. Preferably, the term “antigenic protein” or “immunogenic protein” refers to an (antigenic or immunogenic) protein, which stimulates the body’s adaptive or cellular immune system to provide a humoral or cellular immune response. Therefore, an antigenic / immunogenic protein comprises at least one epitope (as defined herein) or antigen (as defined herein), e.g. selected or derived from a TAA, preferably as described herein.The term “antigenic peptide” or “immunogenic peptide” as used herein preferably refers to a fragment of a full-length antigen, e.g. a fragment of a full-length TAA. Preferably, such a fragment of a full-length antigen comprises or consists of an amino acid sequence, which comprises or consists of a continuous stretch of at least 6, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500 amino acids of a TAA, preferably of a TAA as described herein. More preferably, said fragment is an immunogenic or antigenic fragment of a TAA. In the context of the invention, a preferred fragment of a full-length antigen comprises or consists of an amino acid sequence, which comprises or consists of a continuous stretch of bout 20, 21 , 22, 23, 24, 25, 26, 27, 29, 30, 31 , 32, 33, 34, or 35 amino acids, preferably of 29 amino acids.The term “antigenic peptide” or “immunogenic peptide” as used herein is preferably capable of stimulating an immune response. In particular, the “antigenic peptide” or “immunogenic peptide” as used herein preferably stimulates the body’s adaptive or cellular immune system to provide a humoral or cellular immune response. Therefore, an antigenic / immunogenic peptide comprises at least one epitope from a TAA, preferably an epitope as defined herein, more preferably a B cell or a T cell epitope, even more preferably a T cell epitope.As defined herein, T cell epitopes are typically parts of the antigenic peptides or proteins, such as the at least one antigenic peptide or protein encoded by the artificial nucleic acid described herein, and may comprise fragments of said antigenic peptide or protein, preferably having a length of about 6 to about 20 or even more amino acids, e.g. fragments as processed and presented by MHC class I molecules, preferably having a length of about 8 to about 11 amino acids, e.g. 8, 9, 10, or 11 (or even 12 amino acids), or fragments as processed and presented by MHC class II molecules, preferably having a length of about 13 to about 20 or even more amino acids.According to the present invention, the antigenic peptide or protein is from a TAA, preferably from a TAA as defined herein, or from a variant thereof. A “variant” of a protein, such as a TAA, as used herein ispreferably a polypeptide or protein, having an amino acid sequence which differs from the original sequence of said protein (e.g. a TAA) in one or more mutation(s) / substitution(s), such as one or more substituted, inserted and / or deleted amino acid(s). Such a variant of an amino acid sequence may be, for example, at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the amino acid sequence the variant is derived from. Alternatively, a “variant” of a protein (e.g. a TAA) may have at least 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% amino acid identity over a stretch of at least 10, 15, 30, 50, 75 or 100 amino acids of such protein. Preferably, a variant as used herein has the same, or a comparable specific property. Insertions and substitutions are possible, in particular, at those sequence positions which cause no modification to the three-dimensional structure or do not affect the binding region. Modifications to a three-dimensional structure by insertion(s) or deletion(s) can easily be determined, e.g. using CD spectra (circular dichroism spectra). A variant of a protein may be a functional variant of the protein, which means that the variant exerts essentially the same, or at least 40%, 50%, 60%, 70%, 80%, 90% of the function of the protein it is derived from. Preferably, a variant of a protein (e.g. TAA) as used herein is a functional variant having the same antigenic properties as the protein it is derived from.In preferred embodiments, the present invention thus provides an artificial nucleic acid comprising at least one coding sequence, wherein the at least one coding sequence encodes at least one polypeptide or protein, the at least one polypeptide or protein comprising at least one antigenic peptide or protein from each of the tumour-associated antigens (TAA)- Brevican core protein (BCAN) or a variant thereof,- Neuroligin-4, X-linked (NLGNX4) or a variant thereof,- Receptor-type tyrosine-protein phosphatase zeta (PTPRZ1) or a variant thereof, and- Baculoviral IAP repeat-containing protein 5 (BIRC5) or a variant thereof.In particularly preferred embodiments, said combination of TAAs comprises- Brevican core protein (BCAN; Uniprot PGCB_HUMAN),- Neuroligin 4, X-linked (NLGN4X; Uniprot NLGNX_HUMAN),- Receptor-type tyrosine-protein phosphatase zeta (PTPRZ1 ; Uniprot PTPRZ_HUMAN), and- Baculoviral IAP repeat-containing protein 5 (BIRC5; survivin; Uniprot BIRC5_HUMAN).In some embodiments, the at least one encoded polypeptide or protein further comprises at least one antigenic peptide or protein from the TAA Elongation of very long chain fatty acids protein 2 (ELOVL2; Uniprot ELOV2_HUMAN) or from a variant thereof.Elongation of very long chain fatty acids protein 2 (ELOVL2; Uniprot ELOV2_HUMAN): ELOVL2 is a member of the mammalian microsomal ELOVL fatty acid enzyme family, which is involved in oxidative stress induction and lipid biosynthesis and is responsible for the elongation of very long-chain fatty acids including polyunsaturated fatty acids (PUFAs) required for various cellular functions in mammals. Specifically, ELOVL2 is an essential enzyme for the formation of very-long PUFA in testis.Due to the lack of commonly used abbreviations for the protein of this TAA, the respective abbreviation for the gene name of this TAAs (i.e. ELOVL2) is used throughout the present invention for better readability, i.e. e.g. also in cases where passages refer to the respective polypeptide or protein encoded by the gene.In some embodiments, the artificial nucleic acid sequence comprises at least one coding sequence encoding one polypeptide or protein comprising at least one antigenic peptide or protein from each of BCAN, NLGN4X, PTPRZ1 and BIRC5 (and, optionally, ELOVL2). In other words, the at least one antigenic peptides or proteins from each of BCAN, NLGN4X, PTPRZ1 and BIRC5 (and, optionally, ELOVL2) may all be encoded by one coding sequence and comprised in one and the same polypeptide or protein. Alternatively, the artificial nucleic acid sequence may comprise at least one first coding sequence encoding a first polypeptide or protein comprising at least one antigenic peptide or protein from BCAN, NLGN4X, PTPRZ1 and / or BIRC5 (and, optionally, ELOVL2) and at least one second (or further) coding sequence encoding a second (or further) polypeptide or protein comprising at least one antigenic peptide or protein from BCAN, NLGN4X, PTPRZ1 and / or BIRC5 (and, optionally, ELOVL2), provided that the two (or more) coding sequences together encode the combination of antigenic peptides or proteins as defined herein. Therein, the first coding sequence and the second (or further) coding sequence may be identical or distinct. Preferably, the first coding sequence and the second (or further) coding sequence are distinct and together encode the combination of antigenic peptides or proteins as described herein.In preferred embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein comprising or consisting of an amino acid sequence according to- SEQ ID NO: 124 (BCAN), or an immunogenic fragment or variant thereof,- SEQ ID NO: 125 (NLGNX4), or an immunogenic fragment or variant thereof,- SEQ ID NO: 126 (PTPRZ1), or an immunogenic fragment or variant thereof, and / or - SEQ ID NO: 127 (BIRC5), or an immunogenic fragment or variant thereof.In some embodiments, the at least one encoded polypeptide or protein further comprises at least one antigenic peptide or protein comprising or consisting of an amino acid sequence according to SEQ ID NO: 128 (ELOVL2), or an immunogenic fragment or variant thereof.In preferred embodiments, the at least one encoded polypeptide or protein comprises more than one antigenic peptide from at least one TAA. Preferably, the at least one encoded polypeptide or protein comprises at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 antigenic peptides from at least one of the TAAs BCAN, NLGNX4, PTPRZ1 , BIRC5 or ELOVL2, or from a variant thereof.In preferred embodiments, the at least one encoded polypeptide or protein comprises at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 antigenic peptides from at least one of the TAAs BCAN, NLGNX4, PTPRZ1 , or BIRC5, or from a variant thereof.Preferably, the at least one encoded polypeptide or protein comprises at least two antigenic peptides from PTPRZ1 or from a variant thereof. More preferably, the at least one encoded polypeptide or proteincomprises at least two antigenic peptides from each of PTPRZ1 or from a variant thereof and from BCAN or from a variant thereof.In more preferred embodiments, the at least one encoded polypeptide or protein comprises at least 4 antigenic peptides from PTPRZ1 or from a variant thereof and / or at least 2 antigenic peptides from BCAN or from a variant thereof and / or at least one antigenic peptide from NLGNX4, or from a variant thereof, and / or at least one antigenic peptide from BIRC5, or from a variant thereof.In even more preferred embodiments, the at least one encoded polypeptide or protein comprises at least 4 antigenic peptides from PTPRZ1 or from a variant thereof and at least 2 antigenic peptides from BCAN or from a variant thereof and at least one antigenic peptide from NLGNX4, or from a variant thereof, and at least one antigenic peptide from BIRC5, or from a variant thereof.In preferred embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein comprising or consisting of at least one epitope, preferably as defined herein. Preferably, the at least one antigenic peptide or protein comprising or consisting of at least one epitope comprises or consists of at least one B cell epitope or at least one T-cell epitope, preferably as defined herein. More preferably, the at least one antigenic peptide or protein comprising or consisting of at least one epitope comprises or consists at least one T-cell epitope, preferably as defined herein.In preferred embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein comprising or consisting of at least one T-cell epitope, wherein the at least one antigenic peptide or protein is from each of- BCAN or a variant thereof,- NLGNX4 or a variant thereof,- PTPRZ1 or a variant thereof, and- BIRC5 or a variant thereof.In preferred embodiments, each of the antigenic peptide or proteins comprised in the encoded polypeptide comprises or consists of at least one T-cell epitope, preferably as defined herein. In preferred embodiments, the invention thus provides an artificial nucleic acid comprising at least one coding sequence encoding at least one polypeptide or protein comprising at least one antigenic peptide or protein from each of- BCAN or a variant thereof,- NLGNX4 or a variant thereof,- PTPRZ1 or a variant thereof, and- BIRC5 or a variant thereof, wherein the each of the antigenic peptides or proteins comprises at least one T-cell epitope, preferably as defined herein. Hence, in these embodiments the at least one encoded polypeptide or protein comprises at least one T-cell epitope, preferably as defined herein, of each of BCAN or a variant thereof, NLGNX4 or a variant thereof, PTPRZ1 or a variant thereof, and BIRC5 or a variant thereof.In some embodiments, the at least one encoded polypeptide or protein further comprises at least one antigenic peptide or protein comprising or consisting of at least one T-cell epitope, wherein the at least one antigenic peptide or protein is from ELOVL2 or from a variant thereof. The invention thus also provides an artificial nucleic acid comprising at least one coding sequence encoding at least one polypeptide or protein comprising at least one antigenic peptide or protein from each of- BCAN or a variant thereof,- NLGNX4 or a variant thereof,- PTPRZ1 or a variant thereof,- BIRC5 or a variant thereof, and- ELOVL2 or a variant thereof, wherein the each of the antigenic peptides or proteins comprises at least one T-cell epitope, preferably as defined herein. Hence, in these embodiments the at least one encoded polypeptide or protein comprises at least one T-cell epitope, preferably as defined herein, of each of BCAN or a variant thereof, NLGNX4 or a variant thereof, PTPRZ1 or a variant thereof, BIRC5 or a variant thereof, and ELOVL2 or a variant thereof.In preferred embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein comprising or consisting of at least one major histocompatibility complex class I (MHC-I) epitope.Preferred MHC-I epitopes in the context of BCAN, NLGNX4, PTPRZ1 , BIRC5 and ELOVL2 are as follows:- BCAN: SEQ ID NOs: 130, 365-381 , 518-539, or an immunogenic fragment or variant of any of these;- NLGNX4: SEQ ID NOs: 132, 382-394, 540-547, or an immunogenic fragment or variant of any of these;- PTPRZ1 : SEQ ID NOs: 133-134, 136, 395-489, 548-592, or an immunogenic fragment or variant of any of these;- BIRC5: SEQ ID NOs: 490-510, 593-608, or an immunogenic fragment or variant of any of these;- ELOVL2: SEQ ID NOs: 138, 511-517, 609-622, or an immunogenic fragment or variant of any of these.In preferred embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein comprising or consisting of at least one MHC-I epitope as defined herein, wherein the at least one antigenic peptide or protein is from each of- BCAN or a variant thereof,- NLGNX4 or a variant thereof, and- PTPRZ1 or a variant thereof.In some embodiments, the at least one encoded polypeptide or protein comprises at least one additional antigenic peptide or protein comprising or consisting of at least one MHC-I epitope as defined herein, wherein the at least one additional antigenic peptide or protein is from BIRC5 or from a variant thereof.In preferred embodiments, the at least one encoded polypeptide or protein comprises at least three antigenic peptides, each of the at least three antigenic peptides comprising or consisting of at least one MHC-I epitope from PTPRZ1 or from a variant thereof.In some embodiments, the at least one encoded polypeptide or protein comprises at least four antigenic peptides, each of the at least four antigenic peptides comprising or consisting of at least one MHC-I epitope from PTPRZ1 or from a variant thereof.In some embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein comprising or consisting of at least one MHC-I epitope from ELOVL2 or from a variant thereof.In preferred embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein, the at least one antigenic peptide or protein comprising or consisting of an amino acid sequence according to- SEQ ID NO: 130 (BCA-002) or an immunogenic fragment or variant thereof,- SEQ ID NO: 132 (NLGN4X-001) or an immunogenic fragment or variant thereof,- SEQ ID NO: 133 (PTP-003) or an immunogenic fragment or variant thereof,- SEQ ID NO: 134 (PTP-005) or an immunogenic fragment or variant thereof, and / or- SEQ ID NO: 136 (PTP-013) or an immunogenic fragment or variant thereof.In preferred embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein, the at least one antigenic peptide or protein comprising or consisting of an amino acid sequence according to- SEQ ID NO: 130 (BCA-002) or an immunogenic fragment or variant thereof, and / or- SEQ ID NO: 132 (NLGN4X-001) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 133 (PTP-003) or an immunogenic fragment or variant thereof, or- SEQ ID NO: 134 (PTP-005) or an immunogenic fragment or variant thereof, or- SEQ ID NO: 136 (PTP-013) or an immunogenic fragment or variant thereof.In even more preferred embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein, the at least one antigenic peptide or protein comprising or consisting of an amino acid sequence according to- SEQ ID NO: 130 (BCA-002) or an immunogenic fragment or variant thereof,- SEQ ID NO: 132 (NLGN4X-001) or an immunogenic fragment or variant thereof,- SEQ ID NO: 133 (PTP-003) or an immunogenic fragment or variant thereof,- SEQ ID NO: 134 (PTP-005) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 136 (PTP-013) or an immunogenic fragment or variant thereof.In some embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein comprising or consisting of the amino acid sequence according to SEQ ID NO: 138 (ELCVL2-001) or an immunogenic fragment or variant thereof.“Immunogenic fragments” in the context of any of these sequences preferably means fragments (e.g. N- terminally or C-terminally truncated fragments) of 8 amino acids.In preferred embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein comprising or consisting of at least one major histocompatibility complex class II (MHC- II) epitope.Preferred MHC-II epitopes in the context of BCAN, NLGNX4, PTPRZ1 , BIRC5 are as follows:- BCAN: SEQ ID NOs: 131 , 623-628 or an immunogenic fragment or variant of any of these;- NLGNX4: SEQ ID NOs: 629-640 or an immunogenic fragment or variant of any of these;- PTPRZ1 : SEQ ID NOs: 135, 641-664 or an immunogenic fragment or variant of any of these;- BIRC5: SEQ ID NOs: 137, 665-670, 671 or an immunogenic fragment or variant of any of these.In preferred embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein comprising or consisting of at least one MHC-II epitope, wherein the at least one antigenic peptide or protein is from each of- BIRC5 or a variant thereof, and- PTPRZ1 or a variant thereof, and optionally from- BCAN or a variant thereof.In preferred embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein, the at least one antigenic peptide or protein comprising or consisting of an amino acid sequence according to- SEQ ID NO: 137 (BIR-002) or an immunogenic fragment or variant thereof,- SEQ ID NO: 135 (PTP-010) or an immunogenic fragment or variant thereof, and / or - SEQ ID NO: 131 (BCA-005) or an immunogenic fragment or variant thereof.In preferred embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein, the at least one antigenic peptide or protein comprising or consisting of an amino acid sequence according to- SEQ ID NO: 137 (BIR-002) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 135 (PTP-010) or an immunogenic fragment or variant thereof, and optionally - SEQ ID NO: 131 (BCA-005) or an immunogenic fragment or variant thereof.In preferred embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein, the at least one antigenic peptide or protein comprising or consisting of the amino acid sequences according to- SEQ ID NO: 130 (BCA-002) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 132 (NLGN4X-001) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 133 (PTP-003) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 134 (PTP-005) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 136 (PTP-013) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 137 (BIR-002) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 135 (PTP-010) or an immunogenic fragment or variant thereof, and optionally - SEQ ID NO: 131 (BCA-005) or an immunogenic fragment or variant thereof.In most preferred embodiments, the artificial nucleic acid comprises at least one coding sequence, wherein the at least one coding sequence encodes at least one polypeptide or protein, the at least one polypeptide or protein comprising at least one antigenic peptide or protein from each of the TAAs- Brevican core protein (BCAN) or a variant thereof,- Neuroligin-4, X-linked (NLGNX4) or a variant thereof,- Receptor-type tyrosine-protein phosphatase zeta (PTPRZ1) or a variant thereof, and- Baculoviral IAP repeat-containing protein 5 (BIRC5) or a variant thereof, the at least one antigenic peptide or protein comprising or consisting of the amino acid sequences according to- SEQ ID NO: 130 (BCA-002) or an immunogenic fragment or variant thereof,- SEQ ID NO: 132 (NLGN4X-001) or an immunogenic fragment or variant thereof,- SEQ ID NO: 133 (PTP-003) or an immunogenic fragment or variant thereof,- SEQ ID NO: 134 (PTP-005) or an immunogenic fragment or variant thereof,- SEQ ID NO: 136 (PTP-013) or an immunogenic fragment or variant thereof,- SEQ ID NO: 137 (BIR-002) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 135 (PTP-010) or an immunogenic fragment or variant thereof, and optionally - SEQ ID NO: 131 (BCA-005) or an immunogenic fragment or variant thereof.In some embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein comprising or consisting of the amino acid sequence according to SEQ ID NO: 138 (ELGVL2-001) or an immunogenic fragment or variant thereof.In various embodiments, the at least one encoded polypeptide or protein comprises at least one universal T helper epitope, which may for example be characterized by promiscuous binding to human class II molecules. Preferred universal T helper epitopes in the context of the invention are PTP-010, BIR-002, or BCA-005, which all bind to multiple HLA-DR alleles.In various embodiments, the at least one encoded polypeptide or protein may comprise at least one additional universal T helper epitope that is not comprised in any of the TAAs BIRC5, PTPRZ1 , BCAN, NLGN4X or ELOVL2. Suitable universal T-helper epitopes may be selected from SEQ ID NOs: 3083-3294 of published PCT patent application WO2019008001 , e.g. a synthetic universal T helper epitope (PADRE) or universal T helper epitopes derived from Tetanus or Diphtheria toxoids. Furthermore, the additional universal T helper epitope may also be derived from an HBV core antigen.In preferred embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein from a viral antigen, or from a variant thereof, preferably from Hepatitis B virus (HBV) core antigen or from a variant thereof.In preferred embodiments, such an antigenic peptide or protein from a viral antigen, or from a variant thereof, preferably from Hepatitis B virus (HBV) core antigen or from a variant thereof, is a marker epitope / antigen. Such a marker epitope / antigen can for example give insights firstly about a cancer patient’s immune system general condition / functionality and, secondly, about whether the artificial nucleic acid, preferably formulated as defined in the second aspect, is generally capable of triggering an immune response in a subject. Thirdly, it may be used to monitor vaccine efficacy. Fourthly, the difference between antiviral and antitumor immune response may shed light on occurring cancer immune escape mechanisms in the subject.In preferred embodiments, the at least one antigenic peptide or protein from the viral antigen comprises or consists of at least one MHC-I and / or MHC-II epitope, preferably wherein the at least one antigenic peptide or protein comprises or consists of the amino acid sequence SEQ ID NO: 139 (HBV-001) or an immunogenic fragment or variant thereof.In preferred embodiments, the at least one antigenic peptide or protein from the viral antigen comprises or consists of at least one MHC-I epitope, preferably wherein the at least one antigenic peptide or protein comprises or consists of the amino acid sequence SEQ ID NO: 139 (HBV-001) or an immunogenic fragment or variant thereof. Such an epitope may be used as a marker epitope. In preferred embodiments, the at least one antigenic peptide or protein from the viral antigen additionally comprises or consists of at least one MHC-II epitope, optionally at least one universal T helper epitope. Such an epitope may be used as a marker epitope and / or universal T helper epitope.In various embodiments, the at least one antigenic peptide consists of about 6-500 amino acids, preferably of about 20, 21 , 22, 23, 24, 25, 26, 27, 29, 30, 31 , 32, 33, 34, or 35 amino acids, more preferably of 29 amino acids.In preferred embodiments, the at least one antigenic peptide comprises at least one MHC-I and / or MHC-II epitope, preferably as specified above, wherein the at least one MHC-I and / or MHC-II epitope in the antigenic peptide is flanked N- and C-terminally by amino acid sequences occurring in the respective wild type protein or in a variant thereof, wherein the lengths of the amino acid sequences flanking the at least one MHC-I and / or MHC-II epitope N- or C-terminally, respectively, comprise at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, or 40 amino acid residues.In embodiments, the inclusion of the N- and C-terminal flanking regions may enable correct processing of the antigenic peptide and presentation of the at least one MHC-I and / or MHC-II epitope e.g. upon administration to a cell or subject.The term “amino acid sequences occurring in the respective wild type protein” in this context means the amino acid sequences that the at least MHC-I and / or MHC-II epitope as defined herein is directly surrounded by in the wild type (endogenous) source protein, i.e. TAA or viral antigen. This may allow for asimilar processing of the antigenic peptide or protein and presentation of the of the at least one MHC-I and / or MHC-II epitope as in the wild type (endogenous) source proteins. The term “amino acid sequences occurring in the respective wild type protein or in a variant thereof’ in this context e.g. means amino acid sequences, where the sequences flanking the at least one MHC-I and / or MHC-II epitope are optimized for enhanced processing and presentation compared to the respective wild type protein sequences.In preferred embodiments, the lengths of the amino acid sequences flanking the at least one MHC-I and / or MHC-II epitope N- or C-terminally, respectively, differ from each other by not more than 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19 or 20 amino acid residues, preferably wherein the lengths of the amino acid sequences flanking the at least one MHC-I and / or MHC-II epitope N- or C-terminally are identical.In other terms, the at least one MHC-I and / or MHC-II epitope, should preferably be located in or approximately in a central position of the antigenic peptide, i.e. flanked N- and C-terminally by similar or approximately similar amounts of amino residues. In cases where the antigenic peptide comprises more than one MHC-I and / or MHC-II epitope and this cannot be fulfilled for all of the MHC-I and / or MHC-II epitopes, at least the epitopes NLGN4X-001 , PTP-003, PTP-005, PTP-013, BIR-002, PTP-010, BCA-005, HBV-001 , or ELCVL2-001 are located in or approximately in a central position of the antigenic peptide.In preferred embodiments, wherein the at least one antigenic peptide comprises the MHC-I epitope BCA- 002 and N- and C-terminal flanking regions thereof, the N-terminal flanking region does not comprise the amino sequence aa 446-472 of SEQ ID NO: 124 (BCAN) or any N-terminally truncated fragment thereof with a length of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19 or 20 amino acid residues.Accordingly, for some embodiments, e.g. where the antigenic peptide comprises or consists of an amino acid sequence according to SEQ ID NO: 143 (BCA-002-long) or an immunogenic variant thereof, the MHC- I epitope BCA-002 is not located in or approximately in a central position of the antigenic peptide, but preferably located in the N-terminal half of the antigenic peptide.In preferred embodiments, the lengths of the amino acid sequences flanking the at least one MHC-I and / or MHC-II epitope N- or C-terminally comprise at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid residues.In preferred embodiments, the lengths of the amino acid sequences flanking the most N-terminal and most C-terminal MHC-I and / or MHC-II epitope comprise at least 1 , 2, 3, 4, or 5 amino acid residues.In preferred embodiments, the N- and C-terminally flanking amino acid sequences allow the inclusion of MHC-I and / or MHC-II epitopes other than the MHC-I and / or MHC-II epitopes as specified above or any other MHC-I and / or MHC-II epitopes comprised in any of these.Preferred additional MHC-I epitopes in the context of antigenic peptides comprising N- and C-terminal flanking regions, e.g. of such antigenic peptides with a length of 29 amino acids, are given below for antigenic peptides comprising the indicated epitopes or an immunogenic fragment or variant thereof:- Antigenic peptide comprising SEQ ID NO: 130 (BCA-002): SEQ ID NOs: 518-523;- Antigenic peptide comprising SEQ ID NO: 132 (NLGN4X-001): SEQ ID NOs: 540-547;- Antigenic peptide comprising SEQ ID NO: 133 (PTP-003): SEQ ID NOs: 568-578;- Antigenic peptide comprising SEQ ID NO: 134 (PTP-005): SEQ ID NOs: 548-552;- Antigenic peptide comprising SEQ ID NO: 136 (PTP-013): SEQ ID NOs: 553-567;- Antigenic peptide comprising SEQ ID NO: 137 (BIR-002): SEQ ID NOs: 593-608;- Antigenic peptide comprising SEQ ID NO: 135 (PTP-010): SEQ ID NOs: 579-592;- Antigenic peptide comprising SEQ ID NO: 131 (BCA-005): SEQ ID NOs: 524-539;- Antigenic peptide comprising SEQ ID NO: 138 (ELOVL2-001): SEQ ID NOs: 609-622.A preferred additional MHC-II epitope in the context of antigenic peptides comprising N- and C-terminal flanking regions, e.g. of such antigenic peptides with a length of 29 amino acids, are given below for antigenic peptides comprising the indicated epitope or an immunogenic fragment or variant thereof: - Antigenic peptide comprising SEQ ID NO: 137 (BIR-002): SEQ ID NO: 671 ;In preferred embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein, the at least one antigenic peptide or protein comprising or consisting of an amino acid sequence according to- SEQ ID NO: 143 (BCA-002-long) or an immunogenic fragment or variant thereof,- SEQ ID NO: 145 (NLGN4X-001-long) or an immunogenic fragment or variant thereof,- SEQ ID NO: 146 (PTP-003-long) or an immunogenic fragment or variant thereof,- SEQ ID NO: 147 (PTP-005-long) or an immunogenic fragment or variant thereof,- SEQ ID NO: 149 (PTP-013-long) or an immunogenic fragment or variant thereof,- SEQ ID NO: 150 (BIR-002-long) or an immunogenic fragment or variant thereof,- SEQ ID NO: 148 (PTP-010-long) or an immunogenic fragment or variant thereof,- SEQ ID NO: 144 (BCA-005-long) or an immunogenic fragment or variant thereof, and / or- SEQ ID NO: 152 (HBV-001-long) or an immunogenic fragment or variant thereof.In embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein, the at least one antigenic peptide or protein comprising or consisting of an amino acid sequence according to- SEQ ID NO: 143 (BCA-002-long) or an immunogenic fragment or variant thereof, or- SEQ ID NO: 145 (NLGN4X-001-long) or an immunogenic fragment or variant thereof, or- SEQ ID NO: 146 (PTP-003-long) or an immunogenic fragment or variant thereof, or- SEQ ID NO: 147 (PTP-005-long) or an immunogenic fragment or variant thereof, or- SEQ ID NO: 149 (PTP-013-long) or an immunogenic fragment or variant thereof, or- SEQ ID NO: 150 (BIR-002-long) or an immunogenic fragment or variant thereof, or- SEQ ID NO: 148 (PTP-010-long) or an immunogenic fragment or variant thereof, or- SEQ ID NO: 144 (BCA-005-long) or an immunogenic fragment or variant thereof, or- SEQ ID NO: 152 (HBV-001-long) or an immunogenic fragment or variant thereof.In embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein, the at least one antigenic peptide or protein comprising or consisting of an amino acid sequence according to- SEQ ID NO: 143 (BCA-002-long) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 145 (NLGN4X-001-long) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 146 (PTP-003-long) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 147 (PTP-005-long) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 149 (PTP-013-long) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 150 (BIR-002-long) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 148 (PTP-010-long) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 144 (BCA-005-long) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 152 (HBV-001-long) or an immunogenic fragment or variant thereof.In particularly preferred embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein, the at least one antigenic peptide or protein comprising or consisting of the amino acid sequences according to- SEQ ID NO: 143 (BCA-002-long) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 145 (NLGN4X-001-long) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 146 (PTP-003-long) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 147 (PTP-005-long) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 149 (PTP-013-long) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 150 (BIR-002-long) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 148 (PTP-010-long) or an immunogenic fragment or variant thereof, and, optionally- SEQ ID NO: 144 (BCA-005-long) or an immunogenic fragment or variant thereof, and / or- SEQ ID NO: 152 (HBV-001-long) or an immunogenic fragment or variant thereof.In some embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein comprising or consisting of the amino acid sequence according to SEQ ID NO: 151 (ELOVL2-001-long) or an immunogenic fragment or variant thereof.In preferred embodiments, the at least one encoded polypeptide or protein comprises at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 antigenic peptides from at least one of the TAAs BCAN, NLGNX4, PTPRZ1 , BIRC5 or ELOVL2, or from a variant thereof, wherein the at least 2, 3, 4, 5, 6, 7, 8, 9, or 10, preferably all, antigenic peptides from the same TAA or from the same variant of a TAA are comprised in one encoded polypeptide or protein.In preferred embodiments, the at least 2, 3, 4, 5, 6, 7, 8, 9, or 10, preferably all, antigenic peptides from the same TAA or from the same variant of a TAA are clustered within the one encoded polypeptide or protein.The term “clustered within the one encoded polypeptide or protein” means that antigenic peptides derived from the same TAAs are located together in one “cluster”. Accordingly, the antigenic peptides derived fromthe same TAAs are not separated by an antigen derived from a different TAA. Even though the antigenic peptides derived from the same TAAs are located together in one “cluster”, the individual antigenic peptides derived from the same TAAs may be separated by a linker element as defined below.In preferred embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide comprising or consisting of at least one MHC-II epitope and at least one antigenic peptide comprising or consisting of at least one MHC-I epitope from the same TAA or from the same variant of a TAA, wherein the at least one antigenic peptide comprising or consisting of at least one MHC-II epitope is located N-terminally of the at least one antigenic peptide comprising or consisting of at least one MHC-I epitope.In preferred embodiments in that context, the amino acid sequence according to SEQ ID NO: 131 (BCA- 005) is located N-terminally of the amino acid sequence according to SEQ ID NO: 130 (BCA-002), and / or the amino acid sequence according to SEQ ID NO: 135 (PTP-010) is located N-terminally of the amino acid sequence according to SEQ ID NO: 133 (PTP-003), SEQ ID NO: 134 (PTP-005) and / or SEQ ID NO: 136 (PTP-013).Accordingly, in preferred embodiments in that context, the amino acid sequence according to SEQ ID NO: 144 (BCA-005-long) is located N-terminally of the amino acid sequence according to SEQ ID NO: 143 (BCA-002-long), and / or the amino acid sequence according to SEQ ID NO: 148 (PTP-010-long) is located N-terminally of the amino acid sequence according to SEQ ID NO: 146 (PTP-003-long), SEQ ID NO: 147 (PTP-005-long) and / or SEQ ID NO: 149 (PTP-013-long).In preferred embodiments, the at least one encoded polypeptide or protein comprises at least one linker element, preferably a G4S linker element, wherein the at least one linker element is an amino acid sequence located between two antigenic peptides or proteins, preferably between two antigenic peptides or proteins as defined in herein, or located between an antigenic peptide or protein and an additional amino acid sequence as defined in herein, or located between two additional amino acid sequences as defined in herein.In preferred embodiments, the linker elements are non-immunogenic linker elements.In preferred embodiments, the at least one linker element is a G4S linker element (SEQ ID NO: 196).Further suitable linker elements may be selected from SEQ ID NOs: 2937, 76400-76418, 77018-77058 of published PCT patent application WO2019008001 , said sequences included herewith by reference.In preferred embodiments, where the at least one encoded polypeptide or protein comprises at least two linker elements with the same amino acid sequence, each nucleic acid sequence encoding the same amino acid sequence of the linker elements is different. In preferred embodiments in this context, the nucleic acid sequences encoding for the G4S linker elements are SEQ ID NOs: 280-291 or variants thereof.In preferred embodiments, the at least one encoded polypeptide or protein comprises at least one additional amino acid sequence selected from an immune response activating signal transduction protein located in the external plasma membrane (IRSTepm) or from a variant thereof, preferably wherein this at least one additional amino acid sequence from an IRSTepm or from a variant thereof is located C-terminally of the most C-terminal antigenic peptide or protein, or of a linker element fused C-terminally to said antigenic peptide or protein.A suitable immune response activating signal transduction protein located in the external plasma membrane (IRSTepm) is selected from CTLA4 (Cytotoxic T-lymphocyte protein 4), CD36 (Platelet glycoprotein 4), TRBC2 (T-cell receptor beta-2 chain C region), TRDC (T-cell receptor delta chain C region), TLR4 (Toll-like receptor 4), CD4 (T-cell surface glycoprotein CD4), TRBC1 (T-cell receptor beta-1 chain C region), CD3E (T-cell surface glycoprotein CD3 epsilon chain), PTPRC (Receptor-type tyrosine-protein phosphatase C), FCG3A (Low affinity immunoglobulin gamma Fc region receptor LNP-III-A), CD28 (T-cell- specific surface glycoprotein CD28), CD79A (B-cell antigen receptor complex-associated protein alpha chain), CD19 (B-lymphocyte antigen CD19), NKG2D (NKG2-D type II integral membrane protein), FCERG (High affinity immunoglobulin epsilon receptor subunit gamma), CD79B (B-cell antigen receptor complex- associated protein beta chain), CD86 (T-lymphocyte activation antigen CD86), CD226 (CD226 antigen), MUC17 (Mucin-17), CD209 (CD209 antigen), TLR8 (Toll-like receptor 8), or a variant, fragment or derivative of any of these proteins. In preferred embodiments, the immune response activating signal transduction protein is selected from CTLA4.In various alternative embodiments, at least one additional amino acid sequence selected from a MHC class I trafficking domain (MITD; corresponds to the transmembrane and cytoplasmic domain of the MHC class I molecule) may be used instead of the additional amino acid sequence selected from an IRSTepm. Preferred in this context are SEQ ID NO: 24 or 25 as described in W02020182869, said sequences included herewith by reference.In preferred embodiments in that context, the at least one additional amino acid sequence selected from an IRSTepm or from a variant thereof is an amino acid sequence from CTLA4 or from a variant thereof, preferably the amino acid sequence according to SEQ ID NO: 201 (TM / CD-CTLA4) or a fragment or variant thereof, wherein the amino acid sequence is preferably encoded by a nucleic acid sequence according to SEQ ID NO: 296 or SEQ ID NO: 672, or a fragment or variant thereof.In preferred embodiments, the at least one encoded polypeptide or protein comprises at least one additional amino acid sequence selected from a signal peptide or a variant thereof, preferably wherein the at least one additional amino acid sequence from a signal peptide or a variant thereof is located N-terminally of the most N-terminal antigenic peptide or protein, or N-terminally of a linker element fused N-terminally to said antigenic peptide or protein.Suitable signal peptides may be selected from of SEQ ID NOs: 1 -156, 76948-76951 of published PCT patent application WO2019008001 , said sequences included herewith by reference.In embodiments, the at least one encoded polypeptide or protein comprising the at least one additional amino acid sequence selected from a signal peptide or a variant thereof may additionally comprise 1 , 2, 3, 4 or 5 amino acids C-terminally of the signal peptide or variant thereof as occurring C-terminally of the signal peptide cleavage site in the protein from which the signal peptide or variant thereof is selected.In preferred embodiments in that context, the at least one additional amino acid sequence selected from a signal peptide is from CTLA4 or from a variant thereof, preferably SEQ ID NO: 198 (SP-CTLA4 aa 1-35) or SEQ ID NO: 199 (SP-CTLA4 aa 1-37) or SEQ ID NO: 200 (SP-CTLA4 aa 1-40) or a fragment or variant of any of these.In preferred embodiments, the at least one encoded polypeptide or protein comprises at least one amino acid sequence from a modulator element as further defined in the eighth aspect of the invention.In preferred embodiments, the at least one encoded polypeptide or protein comprises at least one amino acid sequence from a modulator element, wherein the modulator element modulates / impacts the- expression / translation of, and / or- production of, and / or- stability of, and / or- degradation of, and / or- intracellular protein amount of, and / or- turnover of, and / or- processing for presentation by MHC-I and / or MHC-II molecules of, and / or- retention time in endosomal-lysosomal vesicles,- loading of MHC-I and / or MHC-II molecules, and / or- epitope presentation on MHC-I and / or MHC-II molecules, of the at least one encoded polypeptide or protein upon artificial nucleic acid administration, preferably wherein the modulator element is a heterologous sequence element.“Modulation” in this context may e.g. mean an increase or a decrease.In preferred embodiments in that context, the modulator element is a degron.In embodiments in that context, the modulator element is a ubiquitin-dependent degron.In preferred embodiments in that context, the modulator element, preferably a degron, comprises at least one recognition site for an E3 ubiquitin ligase, preferably for a Cullin-RING type E3 ubiquitin ligase, most preferably for a Cul4DCAF12 Cullin-RING type E3 ubiquitin ligase.In preferred embodiments in that context, the modulator element, preferably a degron, is located at the N- terminus of, at the C-terminus of, or within the amino acid sequence of the at least one encoded polypeptide or protein.In preferred embodiments in that context, the degron comprises or consists of an amino acid sequence- of at least 2, 3, 4, or 5, preferably of 5 glutamic acids and is preferably located at the C-terminus of the at least one encoded polypeptide or protein,- of at least 2, 3, 4, or 5, preferably of 5 glycines, and is preferably located at the C-terminus of the at least one encoded polypeptide or protein,- of at least 2, 3, 4, or 5, preferably of 5 arginines, and is preferably located at the N- or C-terminus of the at least one encoded polypeptide or protein, or- of at least 2, 3, 4, or 5, preferably of 5 lysines, and is preferably located at the N-terminus of the at least one encoded polypeptide or protein.In preferred embodiments in that context, the modulator element, preferably a degron, more preferably a degron as defined herein, most preferably a degron comprising or consisting of an amino acid sequence of at least 2, 3, 4, or 5 glutamic acids is located C-terminally of an additional amino acid sequence selected from an IRSTepm, preferably located C-terminally of an additional amino acid sequence from an IRSTepm as defined herein.In even more preferred embodiments, a degron comprising or consisting of an amino acid sequence of at least 2, 3, 4, or 5 glutamic acids, preferably 5 glutamic acids, is located C-terminally of an additional amino acid sequence according to SEQ ID NO: 201 (TM / CD-CTLA4) or a fragment or variant thereof, wherein the amino acid sequence is preferably encoded by a nucleic acid sequence according to SEQ ID NO: 296 or SEQ ID NO: 672, or a fragment or variant thereof.In preferred embodiments, the modulator element is directly located C-terminally of an additional amino acid sequence from an IRSTepm as defined herein, i.e. not separated by any linker element and / or any other amino acid sequence.In preferred embodiments in that context, the at least one encoded polypeptide or protein comprising the modulator element, preferably a degron, is characterized by an increased intracellular protein amount upon artificial nucleic acid administration compared to a corresponding polypeptide or protein without the modulator element.In preferred embodiments in that context, the at least one encoded polypeptide or protein comprising the modulator element, preferably a degron, is characterized by an increased presentation of at least one MHC- II epitope comprised in the at least one encoded polypeptide or protein upon artificial nucleic acid administration compared to a corresponding polypeptide or protein without the modulator element.In preferred embodiments in that context, the at least one encoded polypeptide or protein comprising the modulator element, preferably a degron, is characterized by an increased retention time in endosomal- lysosomal vesicles upon artificial nucleic acid administration compared to a corresponding polypeptide or protein without the modulator element.Preferred polypeptides or proteins of the inventionIn preferred embodiments, the encoded polypeptide or protein comprises, preferably in N- to C-terminal direction, the following elements:• [Antigenic peptide of a TAA] - [G4S - antigenic peptide of a TAA]n and, optionally, [antigenic peptide of a marker antigen] and / or IRSTepm;• SP - [G4S - antigenic peptide of a TAA]n;• SP - [G4S - antigenic peptide of a TAA]n - [antigenic peptide of a marker antigen];• SP - [G4S - antigenic peptide of a TAA]n - [antigenic peptide of a marker antigen] - G4S - IRSTepm;• SP - [G4S - antigenic peptide of a TAA]n - [antigenic peptide of a marker antigen] - G4S - IRSTepm; wherein each may optionally comprise a modulator element as defined herein, wherein n is selected from an integer ranging from 5 to 20, preferably 5 to 15, e.g. 8 and wherein optionally the antigenic peptide of a marker antigen may comprise both a marker MHC-I epitope and a universal T helper epitope.In preferred embodiments, the encoded polypeptide or protein comprises, preferably in N- to C-terminal direction, the following elements:PTPRZ1 (27-55) - G4S - PTPRZ1 (185-213) - G4S - PTPRZ1 (1337-1365) - G4S - PTPRZ1 (1804-1832) - G4S - NLGN4X(121 -149) - G4S - BCAN(92-120) - G4S - BCAN(473-501) - G4S - BIRC5(90-1 18)In preferred embodiments, the encoded polypeptide or protein comprises, preferably in N- to C-terminal direction, the following elements:PTPRZ1 (27-55) - G4S - PTPRZ1 (185-213) - G4S - PTPRZ1 (1337-1365) - G4S - PTPRZ1 (1804-1832) - G4S - NLGN4X(121-149) - G4S - BCAN(92-120) - G4S - BCAN(473-501) - G4S - BIRC5(90-118) - G4S - HBV capsid protein(8-36)In more preferred embodiments, the encoded polypeptide or protein comprises, preferably in N- to C- terminal direction, the following elements:SP-CTLA4(1-35) - G4S - PTPRZ1 (27-55) - G4S - PTPRZ1 (185-213) - G4S - PTPRZ1 (1337-1365) - G4S - PTPRZ1 (1804-1832) - G4S - NLGN4X(121-149) - G4S - BCAN(92-120) - G4S - BCAN(473-501) - G4S - BIRC5(90-118) - G4S - HBV capsid protein(8-36) - G4S - TM / CD-CTLA4(162-223)In even more preferred embodiments, the encoded polypeptide or protein comprises, preferably in N- to C- terminal direction, the following elements:SP-CTLA4(1-35) - G4S - PTPRZ1 (27-55) - G4S - PTPRZ1 (185-213) - G4S - PTPRZ1 (1337-1365) - G4S - PTPRZ1 (1804-1832) - G4S - NLGN4X(121-149) - G4S - BCAN(92-120) - G4S - BCAN(473-501) - G4S - BIRC5(90-118) - G4S - HBV capsid protein(8-36) - G4S - TM / CD-CTLA4(162-223) - 5xGlu C-degronAccordingly, in various embodiments, the at least one encoded polypeptide or protein comprises or consists of the amino acid sequence according to SEQ ID NOs: 156-187, or of an immunogenic fragment or variant of any of these sequences, preferably wherein the immunogenic fragment or variant comprises or consists of an amino acid sequence being at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 156-187.In embodiments, the at least one encoded polypeptide or protein comprises or consists of an amino acid sequence according to- SEQ ID NO: 156 or an immunogenic fragment or variant thereof,- SEQ ID NO: 157 or an immunogenic fragment or variant thereof,- SEQ ID NO: 158 or an immunogenic fragment or variant thereof,- SEQ ID NO: 159 or an immunogenic fragment or variant thereof,- SEQ ID NO: 160 or an immunogenic fragment or variant thereof,- SEQ ID NO: 161 or an immunogenic fragment or variant thereof,- SEQ ID NO: 162 or an immunogenic fragment or variant thereof, or- SEQ ID NO: 163 or an immunogenic fragment or variant thereof.In preferred embodiments, the at least one encoded polypeptide or protein comprises or consists of the amino acid sequence according to SEQ ID NOs: 156, 157, 162, or 163, or of an immunogenic fragment or variant of any of these sequences, preferably wherein the immunogenic fragment or variant comprises or consists of an amino acid sequence being at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 156, 157, 162, or 163.In even more preferred embodiments, the at least one encoded polypeptide or protein comprises or consists of the amino acid sequence according to SEQ ID NOs: 157 or 163, or of an immunogenic fragment or variant of any of these sequences, preferably wherein the immunogenic fragment or variant comprises or consists of an amino acid sequence being at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 157 or 163.In embodiments, the at least one encoded polypeptide or protein comprises or consists of an amino acid sequence according to- SEQ ID NO: 164 or an immunogenic fragment or variant thereof,- SEQ ID NO: 165 or an immunogenic fragment or variant thereof,- SEQ ID NO: 166 or an immunogenic fragment or variant thereof,- SEQ ID NO: 167 or an immunogenic fragment or variant thereof,- SEQ ID NO: 168 or an immunogenic fragment or variant thereof,- SEQ ID NO: 169 or an immunogenic fragment or variant thereof,- SEQ ID NO: 170 or an immunogenic fragment or variant thereof, or- SEQ ID NO: 171 or an immunogenic fragment or variant thereof.In embodiments, the at least one encoded polypeptide or protein comprises or consists of the amino acid sequence according to SEQ ID NOs: 164, 165, 170, or 171 , or of an immunogenic fragment or variant of any of these sequences, preferably wherein the immunogenic fragment or variant comprises or consists of an amino acid sequence being at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 164, 165, 170, or 171.In embodiments, the at least one encoded polypeptide or protein comprises or consists of the amino acid sequence according to SEQ ID NOs: 165 or 171 , or of an immunogenic fragment or variant of any of these sequences, preferably wherein the immunogenic fragment or variant comprises or consists of an amino acid sequence being at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 165 or 171 .In embodiments, the at least one encoded polypeptide or protein comprises or consists of an amino acid sequence according to- SEQ ID NO: 172 or an immunogenic fragment or variant thereof,- SEQ ID NO: 173 or an immunogenic fragment or variant thereof,- SEQ ID NO: 174 or an immunogenic fragment or variant thereof,- SEQ ID NO: 175 or an immunogenic fragment or variant thereof,- SEQ ID NO: 176 or an immunogenic fragment or variant thereof,- SEQ ID NO: 177 or an immunogenic fragment or variant thereof,- SEQ ID NO: 178 or an immunogenic fragment or variant thereof, or- SEQ ID NO: 179 or an immunogenic fragment or variant thereof.In preferred embodiments, the at least one encoded polypeptide or protein comprises or consists of the amino acid sequence according to SEQ ID NOs: 172, 173, 178, or 179, or of an immunogenic fragment or variant of any of these sequences, preferably wherein the immunogenic fragment or variant comprises or consists of an amino acid sequence being at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 172, 173, 178, or 179.In even more preferred embodiments, the at least one encoded polypeptide or protein comprises or consists of the amino acid sequence according to SEQ ID NOs: 172 or 179, or of an immunogenic fragment or variant of any of these sequences, preferably wherein the immunogenic fragment or variant comprises or consists of an amino acid sequence being at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 172 or 179.In embodiments, the at least one encoded polypeptide or protein comprises or consists of an amino acid sequence according to- SEQ ID NO: 180 or an immunogenic fragment or variant thereof,- SEQ ID NO: 181 or an immunogenic fragment or variant thereof,- SEQ ID NO: 182 or an immunogenic fragment or variant thereof,- SEQ ID NO: 183 or an immunogenic fragment or variant thereof,- SEQ ID NO: 184 or an immunogenic fragment or variant thereof,- SEQ ID NO: 185 or an immunogenic fragment or variant thereof,- SEQ ID NO: 186 or an immunogenic fragment or variant thereof, or- SEQ ID NO: 187 or an immunogenic fragment or variant thereof.In preferred embodiments, the at least one encoded polypeptide or protein comprises or consists of the amino acid sequence according to SEQ ID NOs: 180, 181 , 186, or 187, or of an immunogenic fragment or variant of any of these sequences, preferably wherein the immunogenic fragment or variant comprises or consists of an amino acid sequence being at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 180, 181 , 186, or 187.In even more preferred embodiments, the at least one encoded polypeptide or protein comprises or consists of the amino acid sequence according to SEQ ID NOs: 181 or 187, or of an immunogenic fragment or variant of any of these sequences, preferably wherein the immunogenic fragment or variant comprises or consists of an amino acid sequence being at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 181 or 187.In most preferred embodiments, the at least one encoded polypeptide or protein comprises or consists of the amino acid sequence according to SEQ ID NO: 187, or of an immunogenic fragment or variant of this sequence, preferably wherein the immunogenic fragment or variant comprises or consists of an amino acid sequence being at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 187.In preferred embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein from at least one of the TAAs BCAN, NLGNX4, PTPRZ1 , BIRC5 or ELOVL2, or from a variant thereof, comprising or consisting of- at least one MHC-I epitope, wherein the at least one MHC-I epitope is an HLA-A epitope, preferably an HLA-A*02 epitope, more preferably an HLA-A*02:01 epitope, and / or- at least one MHC-II epitope, wherein the at least one MHC-II epitope is an HLA-DR epitope that can be presented by at least one HLA-DR allele, preferably by multiple HLA-DR alleles.In preferred embodiments, the artificial nucleic acid is suitable for vaccination of subjects expressing HLA- A allele HLA-A*02, preferably expressing HLA-A*02:01 .In preferred embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein from at least one of the TAAs BCAN, NLGNX4, PTPRZ1 , BIRC5 or ELOVL2, or from a variant thereof, comprising or consisting of at least one (e.g. a further or additional) MHC-I epitope, wherein the at least one (e.g. a further or additional) MHC-I epitope is an HLA-A / B / C epitope other than a HLA-A*02 or HLA-A*02:01 epitope.In various embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein from at least one of the TAAs BCAN, NLGNX4, PTPRZ1 , BIRC5 or ELOVL2, or from avariant thereof, comprising or consisting of at least one MHC-I epitope binding to one of the following HLA alleles: HLA-A*01 :01 , HLA-A*02:01 , HLA-A*03:01 , HLA-A*11 :01 , HLA-A*24:02, HLA-A*25:01 , HLA- A*26:01 , HLA-A*31 :01 , HLA-A*32:01 , HLA-A*68:01 , HLA-B*07:02, HLA-B*08:01 , HLA-B*13:02, HLA-B*14:02, HLA-B*15:01 , HLA-B*18:01 , HLA-B*27:05, HLA-B*35:01 , HLA-B*35:03, HLA-B*37:01 , HLA-B*38:01 , HLA-B*39:01 , HLA-B*40:01 , HLA-B*40:02, HLA-B*44:02, HLA-B*44:03, HLA-B*49:01 , HLA-B*50:01 , HLA-B*51 :01 , HLA-B*55:01 , HLA-B*56:01 , HLA-B*57:01 , HLA-C*01 :02, HLA-C*02:02, HLA-C*03:03, HLA-C*03:04, HLA-C*04:01 , HLA-C*05:01 , HLA-C*06:02, HLA-C*07:01 , HLA-C*07:02, HLA-C*08:02, HLA-C*12:03.In preferred embodiments, the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein from at least one of the TAAs BCAN, NLGNX4, PTPRZ1 , BIRC5 or ELOVL2, or from a variant thereof, comprising or consisting of at least one MHC-I epitope, wherein the at least one MHC-I epitope is an HLA-A / B / C epitope, wherein HLA-A / B / C is an allele expressed by at least 5, 10, 15, 20, 25, 30, 35, 40, 50, or 60% of the human population in Europe, North America and / or Asia.In preferred embodiments, the artificial nucleic acid is suitable for vaccination of subjects that do not express HLA-A allele HLA-A*02 or HLA-A*02:01 .In preferred embodiments in that context, the at least one MHC-I and / or MHC-II epitope is present or predicted to be present on tumour cells of at least 10%, 20, 30, 40, 50, 60, 70, 80, 90, 95, 96, 97, 98, 99% or 100% of subjects with- glioblastoma and / or astrocytoma,- MGMT-unmethylated glioblastoma and / or astrocytoma with a molecular signature of unmethylated glioblastoma, and / or- “unmethylated” glioblastoma of CNS WHO Grade 4 (according to the 5th edition of the WHO Classification of tumours of the Central Nervous System, Volume 6) and / or isocitrate dehydrogenase (IDH)-wild type astrocytoma with a molecular signature of “unmethylated” glioblastoma, wherein the subjects are optionally newly-diagnosed and / or surgically resected.In preferred embodiments, the artificial nucleic acid is suitable for vaccination of at least 20, 30, 40, 50, 60, 70, 80, 90, 95, 96, 97, 98, 99% or of 100% of the subjects as defined above.In other words, the artificial nucleic acid is suitable for a shared vaccine with regard to the subjects as defined above.In preferred embodiments, the artificial nucleic acid is suitable for inducing a CD8 and / or CD4 immune response in a subject as defined above, wherein the immune response is directed against at least one of the encoded antigenic peptides or proteins from at least one of the TAAs BCAN, NLGNX4, PTPRZ1 , BIRC5 or ELOVL2, or from a variant thereof.In preferred embodiments, the artificial nucleic acid is suitable for inducing a CD8 and / or CD4 immune response in a subject as defined above, wherein the immune response is directed against- at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 MHC-I epitopes from the TAAs, more preferably against at least 1 , 2, 3, 4, 5, or 6 amino acid sequences or immunogenic fragments or variants according to- SEQ ID NO: 130 (BCA-002) or an immunogenic fragment or variant thereof,- SEQ ID NO: 132 (NLGN4X-001) or an immunogenic fragment or variant thereof,- SEQ ID NO: 133 (PTP-003) or an immunogenic fragment or variant thereof,- SEQ ID NO: 134 (PTP-005) or an immunogenic fragment or variant thereof, and / or- SEQ ID NO: 136 (PTP-013) or an immunogenic fragment or variant thereof; and, optionally- SEQ ID NO: 138 (ELOVL2-001) or an immunogenic fragment or variant thereof; and / or- at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 MHC-II epitopes, more preferably against at least 1 , 2, or 3 amino acid sequences or immunogenic fragments or variants according to- SEQ ID NO: 137 (BIR-002) or an immunogenic fragment or variant thereof,- SEQ ID NO: 135 (PTP-010) or an immunogenic fragment or variant thereof, and / or- SEQ ID NO: 131 (BCA-005) or an immunogenic fragment or variant thereof.In preferred embodiments, the artificial nucleic acid is suitable for inducing a CD8 and / or CD4 immune response in a subject as defined above, wherein the immune response is directed against- at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 MHC-I epitopes from the TAAs, more preferably against at least 1 , 2, 3, 4, 5 amino acid sequences or immunogenic fragments or variants according to- SEQ ID NO: 130 (BCA-002) or an immunogenic fragment or variant thereof,- SEQ ID NO: 132 (NLGN4X-001) or an immunogenic fragment or variant thereof,- SEQ ID NO: 133 (PTP-003) or an immunogenic fragment or variant thereof,- SEQ ID NO: 134 (PTP-005) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 136 (PTP-013) or an immunogenic fragment or variant thereof; and- at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 MHC-II epitopes, more preferably against at least 1 , 2, or 3 amino acid sequences or immunogenic fragments or variants according to- SEQ ID NO: 137 (BIR-002) or an immunogenic fragment or variant thereof,- SEQ ID NO: 135 (PTP-010) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 131 (BCA-005) or an immunogenic fragment or variant thereof.In preferred embodiments, the artificial nucleic acid is suitable for inducing a CD8 and / or CD4 immune response in a subject, wherein the immune response is directed against at least one of the encoded antigenic peptides or proteins from the viral antigen as specified herein, in particular from hepatitis B virus (HBV) core antigen or from a variant thereof, preferably against at least 1 , 2, or 3 MHC-I and / or MHC-II epitopes thereof, more preferably against at least the amino sequence according to SEQ ID NO: 139 (HBV- 001), or an immunogenic fragment or variant thereof.In preferred embodiments, the at least one encoded polypeptide or protein does not comprise an antigenic peptide or protein from the TAA ELOVL2 or from a variant thereof.In particularly preferred embodiments, the at least one encoded polypeptide or protein does not comprise the MHC-I epitope ELOVL2-001 (SEQ ID NO: 138) or the antigenic peptide ELOVL2-001-long (SEQ ID NO: 151) or an immunogenic fragment or variant of any of these.In preferred embodiments in this context, where the encoded polypeptide or protein does not comprise an antigenic peptide or protein from the TAA ELOVL2 or from a variant thereof, the at least one encoded polypeptide or protein comprises an additional amino acid sequence selected from an IRSTepm from CTLA4.Nucleic acid sequence features and embodimentsIn the following, suitable features and embodiments referring to the artificial nucleic acids (e.g. DNA or RNA) of the invention are provided and described in detail (e.g. type of nucleic acid, structure of nucleic acid, elements of nucleic acid, modification of nucleic acid etc.). Notably, said features defining nucleic acid as provided in the following may be applied to any nucleic acid in any aspect of the invention (e.g. artificial nucleic acid set, pharmaceutical composition, combination, kit, medical uses, etc.).In embodiments, the at least one coding sequence encodes one polypeptide or protein as defined herein.In preferred embodiments, the nucleic acid of the invention is an artificial nucleic acid.Preferably, the artificial nucleic is selected from an artificial DNA or an artificial RNA.In various embodiments, the artificial nucleic acid, e.g. the RNA, is monocistronic, bicistronic, or multicistronic.In preferred embodiments, the artificial nucleic acid, e.g. the RNA, is selected from a monocistronic nucleic acid or RNA.SuitableAccording to preferred embodiments, the artificial nucleic acid is a bicistronic or a multicistronic nucleic acid, wherein the at least two coding sequences encode at least two polypeptides or proteins, wherein the at least two encoded polypeptides or proteins together comprise the antigenic peptides or proteins as defined herein. In that context, any coding sequence encoding polypeptides or proteins as defined herein, or fragments and variants thereof, may be understood as suitable coding sequence and may therefore be comprised in the artificial nucleic acid of the invention.In preferred embodiments, the artificial nucleic acid is a modified and / or stabilized nucleic acid.According to preferred embodiments, the artificial nucleic acid may thus be provided as a “stabilized nucleic acid” that is to say a nucleic acid showing improved resistance to in vivo degradation and / or a nucleic acid showing improved stability in vivo, and / or a nucleic acid showing improved translatability in vivo. This is particularly important in embodiments where the artificial nucleic acid is an RNA.Preferably, the artificial nucleic acid may be provided as a “stabilized nucleic acid”, e.g. a “stabilized RNA”.In the following, suitable modifications / adaptations are described that are capable of “stabilizing” the artificial nucleic acid, or, in particular, of stabilizing the RNA.In particularly preferred embodiments, the artificial nucleic acid comprises at least one codon modified coding sequence.In preferred embodiments, the at least one coding sequence is a codon modified coding sequence. Suitably, the amino acid sequence encoded by the at least one codon modified coding sequence is not being modified compared to the amino acid sequence encoded by the corresponding wild type or reference coding sequence.The term “codon modified coding sequence” relates to a coding sequence that differs in at least one codon (triplets of nucleotides coding for one amino acid) compared to the corresponding wild type or reference coding sequence. Suitably, a codon modified coding sequence may show improved resistance to in vivo degradation and / or improved stability in vivo, and / or improved translatability in vivo. Codon modifications in the broadest sense make use of the degeneracy of the genetic code wherein multiple codons may encode the same amino acid and may be used interchangeably to optimize / modify the coding sequence for in vivo applications.In particularly preferred embodiments, the at least one coding sequence of the artificial nucleic acid is a codon modified coding sequence, wherein the codon modified coding sequence is selected from C maximized coding sequence, CAI maximized coding sequence, human codon usage adapted coding sequence, G / C content modified coding sequence, and G / C optimized coding sequence, or any combination thereof.In preferred embodiments, the at least one coding sequence is a G / C optimized coding sequence.In preferred embodiments, the at least one coding sequence of the artificial nucleic acid, preferably the RNA, has a G / C content of at least about 50%, 55%, or 60%. In particular embodiments, the at least one coding sequence of the artificial nucleic acid has a G / C content of at least about 50%, 51 %, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61 %, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, or 70%.Advantageously, when transfected into mammalian host cells, the artificial nucleic acid comprising the codon modified coding sequence has a stability of between 12-18 hours, or greater than 18 hours, e.g., 24, 36, 48, 60, 72, or greater than 72 hours and is capable of being expressed by the mammalian host cell.When transfected into mammalian host cells, the artificial nucleic acid comprising the codon modified coding sequence is translated into protein, wherein the amount of protein is at least comparable to, or preferably at least 10% more than, or at least 20% more than, or at least 30% more than, or at least 40% more than, or at least 50% more than, or at least 100% more than, or at least 200% or more than the amount of protein obtained by a naturally occurring or wild type or reference coding sequence transfected into mammalian host cells.In particularly preferred embodiments, the at least one coding sequence may be modified, wherein the G / C content of the at least one coding sequence may be optimized compared to the G / C content of the corresponding wild type or reference coding sequence (“G / C optimized coding sequence”). “Optimized” in that context refers to a coding sequence wherein the G / C content is preferably increased to the essentially highest possible G / C content. The generation of a G / C content optimized nucleic acid sequence may be carried out using a method according to W02002098443. In this context, the disclosure of W02002098443 is included in its full scope in the present invention. G / C optimized coding sequences are indicated by the abbreviations “opt1 ”.In some embodiments, the at least one coding sequence may be modified, wherein the C content of the at least one coding sequence may be increased, preferably maximized, compared to the C content of the corresponding wild type or reference coding sequence (“C maximized coding sequence”). The generation of a C maximized nucleic acid sequences may suitably be carried out using a modification method according to WO2015062738. In this context, the disclosure of WO2015062738 is included herewith by reference.In embodiments, the at least one coding sequence may be modified, wherein the codons in the at least one coding sequence may be adapted to human codon usage (“human codon usage adapted coding sequence”). Codons encoding the same amino acid occur at different frequencies in humans. Accordingly, the coding sequence of the nucleic acid is preferably modified such that the frequency of the codons encoding the same amino acid corresponds to the naturally occurring frequency of that codon according to the human codon usage.In embodiments, the at least one coding sequence may be modified, wherein the G / C content of the at least one coding sequence may be modified compared to the G / C content of the corresponding wild type or reference coding sequence (“G / C modified coding sequence”). In this context, the terms “G / C optimization” or “G / C content modification” relate to a nucleic acid that comprises a modified, preferably an increased number of guanosine and / or cytosine nucleotides as compared to the corresponding wild type or reference coding sequence. Such an increased number may be generated by substitution of codons containing adenosine or thymidine nucleotides by codons containing guanosine or cytosine nucleotides.In embodiments, the at least one coding sequence may be modified, wherein the codon adaptation index (CAI) may be increased or preferably maximised in the at least one coding sequence (“CAI maximized coding sequence”). It is preferred that all codons of the wild type or reference nucleic acid sequence that are relatively rare in e.g. a human are exchanged for a respective codon that is frequent in the e.g. a human, wherein the frequent codon encodes the same amino acid as the relatively rare codon. Suitably, the most frequent codons are used for each amino acid of the encoded protein (see Table 2 of WO2021156267, most frequent human codons are marked with asterisks). Suitably, the codon adaptation index (CAI) of the at least one coding sequence is at least 0.5, at least 0.8, at least 0.9 or at least 0.95, most preferably 1 (CAM).In preferred embodiments, the at least one coding sequence comprises or terminates with more than one stop codon to allow sufficient termination of translation. In particularly preferred embodiments, the at least one coding sequence comprises two or three stop codons to allow sufficient termination of translation. These more than one stop codons may optionally be positioned in alternative reading frames.UTRs:In preferred embodiments, the artificial nucleic acid, preferably the RNA, comprises at least one untranslated region (UTR) or UTR element.The terms “untranslated region” or “UTR” or “UTR element” are intended to refer to a part of a nucleic acid molecule typically located 5’ or 3’ of a coding sequence. An UTR is not translated into protein. An UTR may be part of the nucleic acid, e.g. an RNA. An UTR may comprise elements for controlling gene expression, also called regulatory elements. Such regulatory elements may be, e.g., ribosomal binding sites, miRNA binding sites, promotor elements etc. Regulatory sequence elements may determine turnover, stability, and localization of the nucleic acid, in particular the RNA. Moreover, UTRs may harbour sequence elements that enhance translation.In medical applications, translation of the nucleic acid into at least one peptide or protein is of paramount importance to therapeutic efficacy. Certain combinations of 3’-UTR elements and / or 5 -UTR elements may enhance the expression of operably linked coding sequences encoding peptides or proteins as defined herein. Nucleic acid molecules harbouring said UTR combinations advantageously enable rapid and transient expression of encoded tumour antigens after administration to a subject. Said 5’-UTRs or 3’-UTRs may be derived from naturally occurring genes or may be synthetically engineered.In preferred embodiments, the artificial nucleic acid comprises at least one coding sequence as defined herein operably linked to at least one 3’-UTR element and / or at least one 5 -UTR element.Preferably, the at least one UTR element is selected from at least one 5’-UTR and / or at least one 3 -UTR, preferably selected from at least one heterologous 5’-UTR and / or at least one heterologous 3’-UTR.The term “heterologous” sequence or “heterologous” UTR as used herein is intended to refer to a nucleic acid sequence or UTR that is not from the same gene or the same genomic fusion or the same naturally occurring transcript. Accordingly, a heterologous sequences or heterologous UTRs may be derivable from the same organism (e.g. human) or from a different organism. Heterologous sequences or heterologous UTRs do naturally (in nature) not occur in the same nucleic acid.In preferred embodiments, the artificial nucleic acid comprises at least one 3’-UTR element.The terms “3’-untranslated region” or “3 -UTR” or “3’-UTR element” refer to a part of a nucleic acid molecule located 3’ (i.e. downstream) of a coding sequence and which is not translated into protein. A 3’-UTR may be part of a nucleic acid located between a coding sequence and an (optional) terminal poly(A) sequence. A 3 -UTR may comprise elements for controlling gene expression, also called regulatory elements. Such regulatory elements may be, e.g., ribosomal binding sites, miRNA binding sites.Preferably, the artificial nucleic acid comprises at least one 3’-UTR element, which may be derivable from a gene that relates to an RNA with enhanced half-life (i.e. that provides a stable RNA).In some embodiments, the 3 -UTR element comprises one or more of a polyadenylation signal, a binding site for proteins that affect nucleic acid stability or location in a cell, or one or more miRNA or binding sites for miRNAs.In preferred embodiments, the artificial nucleic acid comprises at least one 3’-UTR element, wherein the at least one 3’-UTR comprises or consists of a nucleic acid sequence derived or selected from a 3’-UTR of a gene selected from PSMB3, ALB7, alpha-globin, beta-globin, ANXA4, CASP1 , COX6B1 , FIG4, GNAS, NDUFA1 , RPS9, SLC7A3, TUBB4B, AES+12S ribosomal RNA / mitochondrion, or from a homolog, a fragment, or variant of any one of these genes.In preferred embodiments, the at least one 3’-UTR element that is derived or selected from PSMB3, ALB7, alpha-globin, beta-globin, ANXA4, CASP1 , COX6B1 , FIG4, GNAS, NDUFA1 , RPS9, SLC7A3, TUBB4B comprises or consist of a nucleic acid sequence being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 66-95, 112-123, or a fragment or a variant of any of these.In other embodiments, the at least one 3’-UTR element comprises or consist of a nucleic acid sequence being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 96-111 , or a fragment or a variant of any of these.In particularly preferred embodiments, the artificial nucleic acid comprises a 3 -UTR element derived or selected from a PSMB3 gene, wherein the at least one 3’-UTR element comprises or consists of a nucleic acid sequence being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%,94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 66, 67, 112-123, or a fragment or a variant thereof, preferably SEQ ID NO: 67, or a fragment or a variant thereof.In preferred embodiments, the artificial nucleic acid comprises at least one 5’-UTR element.The terms “5’-untranslated region” or “5’-UTR” or “5’-UTR element” refer to a part of a nucleic acid located 5’ (i.e. “upstream”) of a coding sequence and which is not translated into protein. A 5’-UTR may be part of a nucleic acid located 5’ of the coding sequence. Typically, a 5’-UTR starts with the transcriptional start site and ends before the start codon of the coding sequence. A 5’-UTR may comprise elements for controlling gene expression, called regulatory elements. Such regulatory elements may be, e.g., ribosomal binding sites, miRNA binding sites etc..Preferably, the artificial nucleic acid comprises at least one 5’-UTR element, which may be derivable from a gene that relates to an RNA with enhanced half-life (i.e. that provides a stable RNA).In some embodiments, the 5’-UTR element comprises one or more of a binding site for proteins that affect nucleic acid stability or location in a cell, or one or more miRNA or binding sites for miRNAs.In preferred embodiments, the artificial nucleic acid comprises at least one 5’-UTR element, wherein the at least one 5’-UTR comprises a nucleic acid sequence derived or selected from a 5’-UTR of gene selected from HSD17B4, RPL32, AIG1 , alpha-globin, ASAH1 , ATP5A1 , COX6C, DPYSL2, MDR, MP68, NDUFA4, NOSIP, RPL31 , RPL35A, SLC7A3, TUBB4B, UBQLN2, synthetic origin, or from a homolog, a fragment or variant of any one of these genes.In preferred embodiments, the at least one 5’-UTR element that is derived or selected from HSD17B4, RPL32, AIG1 , alpha-globin, ASAH1 , ATP5A1 , COX6C, DPYSL2, MDR, MP68, NDUFA4, NOSIP, RPL31 , RPL35A, SLC7A3, TUBB4B, UBQLN2 comprises or consist of a nucleic acid sequence being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 12-45, 64, 65, or a fragment or a variant of any of these.In other embodiments, the at least one 5’-UTR element comprises or consist of a nucleic acid sequence being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 46-63, or a fragment or a variant of any of these.In particularly preferred embodiments, the artificial nucleic acid comprises a 5’-UTR element derived or selected from a HSD17B4 gene, wherein the at least one 5’-UTR comprises or consists of a nucleic acid sequence being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 12, 13, 64, 65, or a fragment or a variant thereof, preferably SEQ ID NO: 13, or a fragment or a variant thereof.In various embodiments, the artificial nucleic acid, preferably the RNA, comprises at least one coding sequence as specified herein, operably linked to a 3’-UTR element and / or a 5’-UTR element selected from the following 5’-UTR / 3’-UTR combinations (“also referred to UTR designs”): a-1 (HSD17B4 / PSMB3), a-2 (NDUFA4 / PSMB3), a-3 (SLC7A3 / PSMB3), a-4 (NOSIP / PSMB3), a-5 (MP68 / PSMB3), b-1 (UBQLN2 / RPS9), b-2 (ASAH1 / RPS9), b-3 (HSD17B4 / RPS9), b-4 (HSD17B4 / CASP1), b-5 (NOSIP / COX6B1), c-1 (NDUFA4 / RPS9), c-2 (NOSIP / NDUFA1), c-3 (NDUFA4 / COX6B1), c-4 (NDUFA4 ZNDUFA1), c-5 (ATP5A1 / PSMB3), d-1 (RPL31 / PSMB3), d-2 (ATP5A1 / CASP1), d-3 (SLC7A3 / GNAS), d-4 (HSD17B4 / NDUFA1), d-5 (SLC7A3 / NDUFA1), e-1 (TUBB4B / RPS9), e-2 (RPL31 / RPS9), e-3 (MP68 / RPS9), e-4 (NOSIP / RPS9), e-5 (ATP5A1 / RPS9), e-6 (ATP5A1 / COX6B1), f-1 (ATP5A1 / GNAS), f-2 (ATP5A1 / NDUFA1), f-3 (HSD17B4 / COX6B1), f-4 (HSD17B4 / GNAS), f-5 (MP68 / COX6B1), g-1 (MP68 / NDUFA1), g-2 (NDUFA4 / CASP1), g-3 (NDUFA4 / GNAS), g-4 (NOSIP / CASP1), g-5(RPL31 / CASP1), h-1 (RPL31 / COX6B1), h-2 (RPL31 / GNAS), h-3 (RPL31 / NDUFA1), h-4(SLC7A3 / CASP1), h-5 (SLC7A3 / COX6B1), i-1 (SLC7A3 / RPS9), i-2 (RPL32 / ALB7), i-2 (RPL32 / ALB7), or i-3 (alpha-globin gene).In preferred embodiments, the at least one 5’-UTR element is selected from HSD17B4 and the at least one 3’-UTR element is selected from PSMB3.Accordingly, in particularly preferred embodiments, the artificial nucleic acid, preferably the RNA, comprises at least one coding sequence as defined herein, wherein said coding sequence is operably linked to a HSD17B4 5’-UTR element and a PSMB3 3’-UTR element (HSD17B4 / PSMB3 (a-1)). It has been shown by the inventors that this embodiment is particularly beneficial for expressing the tumour antigen combination in human cells.In preferred embodiments, the A / U (A / T) content in the environment of the ribosome binding site of the nucleic acid is increased compared to the A / U (A / T) content in the environment of the ribosome binding site of its respective wild type or reference nucleic acid. This modification increases the efficiency of ribosome binding to the nucleic acid, which is in turn beneficial for an efficient translation of the nucleic acid into peptides or proteins.Accordingly, in a particularly preferred embodiment, the artificial nucleic acid comprises a ribosome binding site, also referred to as “Kozak sequence”, that is identical to or at least 80%, 85%, 90%, 95% identical to any one of SEQ ID NOs: 1 or 2, or sequences GCCGCCACC (DNA), GCCGCCACC (RNA), GCCACC (DNA), GCCACC (RNA), ACC (DNA) or ACC (RNA), or fragments or variants of any of these, preferably ACC (RNA).DNA and RNA constructs:In preferred embodiments, the artificial nucleic acid is an isolated nucleic acid. The term “isolated nucleic acid” does not encompass a cell or a subject that comprises said nucleic acid, but relates to the nucleic acid as an isolated molecule or ensemble of isolated molecules. For example, the “isolated nucleic acid”can be isolated or purified from a cell, or can be a nucleic acid (e.g. RNA) isolated from an RNA in vitro transcription.In preferred embodiments, the artificial nucleic acid is a therapeutic nucleic acid. Accordingly, the nucleic acid is suitable for a use in a therapeutic context, in particular to provide the combination of tumour antigens.In embodiments, the artificial nucleic acid is selected from a DNA or an RNA.In embodiments, the at least one nucleic acid is selected from a DNA.The DNA may be any type of DNA that comprises a coding sequence as defined herein including any type of single stranded DNA, any type of double stranded DNA, any type of linear DNA, and any type of circular DNA.A suitable DNA may be selected from bacterial plasmid, an adenovirus, a poxvirus, a parapoxivirus (orf virus), a vaccinia virus, a fowlpox virus, a herpes virus, an adeno-associated virus (AAV), an alphavirus, a lentivirus, a lambda phage, a lymphocytic choriomeningitis virus and a Listeria sp, Salmonella sp..In preferred embodiments, the DNA is selected from a viral DNA, preferably an adeno-associated virus DNA.In particularly preferred embodiments, the at least one nucleic acid is selected from an RNA.The RNA may be any type of RNA that comprises a coding sequence as defined herein including any type of single stranded RNA, any type of double stranded RNA, any type of linear RNA, and any type of circular RNA.In preferred embodiments, the RNA may be any type of RNA that comprises a coding sequence as defined herein including any type of single stranded RNA, any type of double stranded RNA, any type of linear RNA, and any type of circular RNA.In preferred embodiments, the RNA is selected from mRNA, circular RNA, replicon RNA or self-replicating RNA, or viral RNA.In preferred embodiments, the RNA is a circular RNA. As used herein, “circular RNA” or “circRNAs” have to be understood as an RNA construct that is connected to form a circle and therefore does not comprise a 3’ or 5’ terminus. In preferred embodiments, said circRNA comprises at least one coding sequence encoding at least one tumour antigen as defined herein. Preferred circular RNA construct designs in the context of the invention can be taken from WO2023073228, in particular claims 1 to 51 of WO2023073228.In preferred embodiments, the RNA is a replicon RNA. The term “replicon RNA” or “self-replicating RNA” will be recognized and understood by the person of ordinary skill in the art and is preferably intended to be an optimized self-replicating RNA. Such constructs may include replicase elements derived from e.g. alphaviruses (e.g. SFV, SIN, VEE, or RRV) and the substitution of the structural virus proteins with the nucleic acid of interest (that is, the sequence encoding at least one tumour antigen).In particularly preferred embodiments, the artificial nucleic acid is selected from an mRNA. mRNA is preferred to provide the combination of tumour antigens according to the invention, because mRNA allows for regulated dosage, transient expression, complete degradation of the mRNA after protein synthesis, and does not pose the risk of insertional mutations.Preferably, the artificial nucleic acid, preferably the RNA, comprises about 50 to about 20000 nucleotides, or about 500 to about 10000 nucleotides, or about 1000 to about 10000 nucleotides, or preferably about 1000 to about 5000 nucleotides, or even more preferably about 2000 to about 5000 nucleotides.In preferred embodiments, the artificial nucleic acid comprises at least one poly(N) sequence, e.g. at least one poly(A) sequence, at least one poly(U) sequence, at least one poly(C) sequence, or combinations thereof.In preferred embodiments, the artificial nucleic acid, e.g. the RNA, comprises at least one poly(A) sequence. In some embodiments, the artificial nucleic acid comprises least two, three, or more poly(A) sequences.The terms “poly(A) sequence”, “poly(A) tail” or “3’-poly(A) tail” as used herein refer to a sequence of adenosine nucleotides, typically located at the 3’-end of a linear RNA of up to about 1000 adenosine nucleotides. Preferably, said poly(A) sequence is essentially homopolymeric, e.g. a poly(A) sequence of 100 adenosine nucleotides has essentially the length of 100 nucleotides. In other embodiments, the poly(A) sequence may be interrupted by at least one nucleotide different from an adenosine nucleotide, e.g. a poly(A) sequence of 100 adenosine nucleotides may have a length of more than 100 nucleotides (comprising 100 adenosine nucleotides and in addition said at least one nucleotide - or a stretch of nucleotides - different from an adenosine nucleotide).In preferred embodiments, the at least one poly(A) sequence may comprise about 20 to about 500 adenosine nucleotides, about 40 to about 250 adenosine nucleotides, about 60 to about 250 adenosine nucleotides, preferably about 60 to about 150 adenosine nucleotides. Suitably, the length of the poly(A) sequence may be at least about or even more than about 10, 50, 64, 75, 100, 200, 300, 400, or 500 adenosine nucleotides, preferably consecutive adenosine nucleotides.In particularly preferred embodiments, the at least one poly(A) sequence comprises about 100 adenosine nucleotides (A100), preferably about 100 consecutive adenosine nucleotides.In further embodiments, the artificial nucleic acid comprises at least one interrupted poly(A) sequence comprising about 100 adenosine nucleotides, wherein the poly(A) sequence is interrupted by nonadenosine nucleotides, preferably by about 10 non-adenosine (N10) nucleotides. In that context, a poly(A) sequence A30-N10-A70 is preferred.Accordingly, in embodiments, the artificial nucleic acid, preferably the RNA, comprises at least two poly(A) sequences.In preferred embodiments, the at least one poly(A) sequence is located directly at the 3’ terminus of the nucleic acid, preferably the RNA. In preferred embodiments, the 3’-terminal nucleotide (that is the last 3’- terminal nucleotide in the polynucleotide chain) is the 3’-terminal A nucleotide of the at least one poly(A) sequence. The term “directly located at the 3’ terminus” has to be understood as being located exactly at the 3’ terminus - in other words, the 3’ terminus of the nucleic acid consists of a poly(A) sequence terminating with an A.Ending on an adenosine nucleotide decreases the induction of interferons, e.g. IFN-alpha, by the RNA of the invention if for example administered as a medicament to a human. This is important as the induction of interferons, e.g. IFNalpha, is thought to be one main factor for induction of side effects.Accordingly, in particularly preferred embodiments, the artificial nucleic acid, preferably the RNA, comprises a poly(A) sequence of about 100 consecutive adenosine nucleotides, wherein said poly(A) sequence is located directly at the 3’ terminus of the RNA, optionally wherein the 3’ terminal nucleotide is an adenosine.In preferred embodiments, the poly(A) sequence of the nucleic acid, e.g. the RNA, is obtained from a DNA template during RNA in vitro transcription. In other embodiments, the poly(A) sequence is obtained in vitro by common methods of chemical synthesis without being necessarily transcribed from a DNA template. In other embodiments, poly(A) sequences are generated by enzymatic polyadenylation of the RNA (after RNA in vitro transcription) using e.g. immobilized poly(A)polymerases according to WO2016174271 .In some embodiments, the artificial nucleic acid, e.g. the RNA, comprises at least one poly(A) sequence obtained by enzymatic polyadenylation, wherein the majority of RNA molecules comprise about 100 (+ / - 20) to about 500 (+ / - 100) adenosine nucleotides, preferably about 100 (+ / - 20) to about 200 (+ / - 40) adenosines.In some embodiments, the artificial nucleic acid comprises at least one polyadenylation signal.In preferred embodiments, the artificial nucleic acid comprises at least one poly(C) sequence and / or at least one miRNA binding site and / or histone stem-loop sequence.In some embodiments, the 3 -UTR element and / or the 5’-UTR element comprises one or more miRNA or binding sites for miRNAs. MicroRNAs (or miRNA) are 19-25 nucleotide long noncoding RNAs that bind to the 3’-UTR of RNA molecules and down-regulate gene expression either by reducing RNA stability or by inhibiting translation. E.g., microRNAs are known to regulate RNA, and thereby protein expression, e.g. in liver (miR-122), heart (miR-ld, miR-149), endothelial cells (miR-17-92, miR-126), adipose tissue (let-7, miR- 30c), kidney (miR-192, miR-194, miR-204), myeloid cells (miR-142-3p, miR-142-5p, miR-16, miR-21 , miR- 223, miR-24, miR-27), muscle (miR-133, miR-206, miR-208), and lung epithelial cells (let-7, miR-133, miR- 126). The RNA may comprise one or more microRNA target sequences, microRNA sequences, or microRNA seeds. Such sequences may correspond to any known microRNA, e.g. to those taught in US20050261218 and US20050059005.Accordingly, miRNA, or binding sites for miRNAs as defined above may be removed from the 3’-UTR or 5’- UTR or may be introduced into the 3’-UTR or 5’-UTR in order to tailor the expression to desired cell types or tissues.In some embodiments, the artificial nucleic acid comprises at least one poly(C) sequence. A poly(C) sequence in the context of the invention may be located in an UTR region, preferably in the 3’ UTR.The term “poly(C) sequence” as used herein is intended to be a sequence of cytosine nucleotides of up to about 200 cytosine nucleotides. In preferred embodiments, the poly(C) sequence comprises about 10 to about 200 cytosine nucleotides, about 10 to about 100 cytosine nucleotides, about 20 to about 70 cytosine nucleotides, about 20 to about 60 cytosine nucleotides, or about 10 to about 40 cytosine nucleotides. In a particularly preferred embodiment, the poly(C) sequence comprises about 30 cytosine nucleotides.In preferred embodiments, the artificial nucleic acid, e.g. the RNA, comprises at least one histone stemloop (hSL) or histone stem-loop structure. A hSL in the context of the invention may be located in an UTR region, preferably in the 3 -UTR.The term “histone stem-loop” (hSL) is intended to refer to nucleic acid sequences that forms a stem-loop secondary structure predominantly found in histone mRNAs. Histone stem-loop sequences / structures may suitably be selected from hSL sequences as disclosed in W02012019780. A hSL sequence that may be used herein may be derived from formulae (I) or (II) of W02012019780. Accordingly, the artificial nucleic acid may comprise at least one hSL sequence derived from the specific formulae (la) or (Ila) of WO2012019780.In preferred embodiments, the artificial nucleic acid, e.g. the RNA, comprises at least one histone stemloop sequence, wherein said histone stem-loop sequence comprises or consists of a nucleic acid sequence identical or at least 70%, 80%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 3 or 4, or a fragment or variant of any of these. Preferably, the histone stem-loop sequence comprises or consists of a nucleic acid sequence according to SEQ ID NO: 4, or a fragment or thereof.In other embodiments, the artificial nucleic acid does not comprise a histone stem-loop as defined herein.In preferred embodiments, the artificial nucleic acid comprises a 3’-terminal sequence element. The 3’- terminal sequence element represents the 3’ terminus of the RNA. A 3’-terminal sequence element may comprise at least one poly(N) sequence as defined herein and, optionally, at least one hSL as defined herein.In preferred embodiments, the artificial nucleic acid comprises at least one 3’-terminal sequence element comprising or consisting of an RNA sequence being identical or at least 70%, 80%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 5-11 , or a fragment or variant of these sequences.In preferred embodiments, the artificial nucleic acid comprises a 3’-terminal sequence element comprising a hSL as defined herein followed by a poly(A) sequence comprising about 100 consecutive adenosines.In particularly preferred embodiments, the artificial nucleic acid comprises a 3’-terminal sequence element comprising or consisting of a nucleic acid sequence being identical or at least 70%, 80%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 5 or 6, or a fragment or variant thereof.In some embodiments, the artificial nucleic acid comprises a 5’-terminal sequence element comprising or consisting of a nucleic acid sequence being identical or at least 70%, 80%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of sequences AGGAGA, GGGAGA, GGGAAA, AGAAUA, AGAUUA, GAUGGG or GGGCG, or a fragment or variant of these sequences.In preferred embodiments, the artificial nucleic acid comprises a 5’-terminal sequence element comprising or consisting of a nucleic acid sequence being identical or at least 70%, 80%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to sequence AGGAGA, or a fragment or variant thereof.Such a 5’-terminal sequence element may comprise e.g. a binding site for T7 RNA polymerase. Further, the first nucleotide of said 5’-terminal start sequence may preferably comprise a 2’0 methylation, e.g. 2’0 methylated guanosine or a 2’0 methylated adenosine.Modified nucleotides:According to various embodiments, the artificial nucleic acid, preferably the RNA, is modified, wherein the modification preferably refers to chemical modifications comprising backbone modifications as well as sugar modifications or base modifications.A modified nucleic acid or RNA may comprise nucleotide analogues / modifications, e.g. backbone modifications, sugar modifications or base modifications. A backbone modification is a modification in which phosphates of the backbone of the nucleotides of the RNA are chemically modified. A sugar modificationis a chemical modification of the sugar of the nucleotides of the RNA. Furthermore, a base modification is a chemical modification of the base moiety of the nucleotides of the RNA. In this context, nucleotide analogues or modifications are preferably selected from nucleotide analogues which are applicable for transcription and / or translation.In embodiments, the artificial nucleic acid, preferably the RNA, comprises at least one modified nucleotide.In some embodiments, the at least one modified nucleotide is selected from pseudouridine, N1 - methylpseudouridine, N1 -ethylpseudouridine, 2-thiouridine, 4’-thiouridine, 5-methylcytosine, 5- methyluridine, 2-th i o-1 -methyl-1 -deaza-pseudouridine, 2-th io- 1 -methyl-pseudouridine, 2-thio-5-aza- uridine, 2-thio-dihydropseudouridine, 2-thio-dihydrouridine, 2-thio-pseudouridine, 4-methoxy-2-thio- pseudouridine, 4-methoxy-pseudouridine, 4-thio-1 -methyl-pseudouridine, 4-thio-pseudouridine, 5-aza- uridine, dihydropseudouridine, 5-methoxyuridine and 2’-O-methyl uridine.Particularly preferred in that context are pseudouridine (qj) and N1 -methylpseudouridine (m1 qj). Accordingly, in preferred embodiments, the artificial nucleic acid is an RNA that comprises at least one modified nucleotide, preferably a modified nucleotide selected from pseudouridine (qj) or N1 - methylpseudouridine (m1 qj). In particularly preferred embodiments, the at least one modified nucleotide is N1 -methylpseudouridine (m1 qj).In some embodiments, essentially all, e.g. essentially 100% of the uracil in the coding sequence (or the full nucleic acid sequence) have a chemical modification, preferably a chemical modification in the 5-position of the uracil.In preferred embodiments, the artificial nucleic acid is a modified RNA wherein each uracil is substituted by a modified nucleotide. Accordingly, in preferred embodiments, 100% of the uracil in the full nucleic acid sequence, preferably the RNA sequence, are substituted with a modified nucleotide, preferably N1 - methylpseudouridine (m1 qj). Alternatively, 100% of the uracil in the full nucleic acid sequence, preferably the RNA sequence, are substituted with pseudouridine (qj).In equally preferred embodiments, the artificial nucleic acid, preferably the RNA, does not comprise modified nucleotides such as chemically modified nucleotides. Notably, a 5’-cap structure as defined below is typically not considered to be a chemically modified nucleotide. Accordingly, the artificial nucleic acid, preferably the RNA, comprises a sequence that consists only of G, C, A and U nucleotides and therefore does not comprise modified nucleotides, and optionally comprises a 5’-cap structure. In embodiments, the artificial nucleic acid, preferably the RNA, does not comprise N1 -methylpseudouridine (mi l1) substituted positions or pseudouridine (qj) substituted positions.RNA constructs that do not comprise chemically modified nucleotides may be beneficial in the context of cancer therapies as stronger T-cell responses can be induced by providing the cancer antigens via nonmodified RNA (compared to m1 qj or qj modified RNA).Cap structures:In preferred embodiments, the artificial nucleic acid is an RNA that comprises a 5’-cap structure.Such a 5’-cap structure suitably stabilizes the nucleic acid and / or enhances expression of the encoded tumour antigen and / or reduces the stimulation of the innate immune system after administration.Accordingly, in preferred embodiments, the artificial nucleic acid, preferably the RNA, comprises a 5’-cap structure, preferably m7G, capO, cap1 , cap2, a modified capO or a modified cap1 structure.The term “5’-cap structure” refers to a 5’ modified nucleotide, particularly a guanine nucleotide, positioned at the 5’-end of an RNA. Preferably, the 5’-cap structure is connected via a 5’-5’-triphosphate linkage to the RNA.5’-cap structures which may be suitable in the context of the present invention are capO (methylation of the first nucleobase, e.g. m7GpppN), cap1 (additional methylation of the ribose of the adjacent nucleotide of m7GpppN), cap2 (additional methylation of the ribose of the 2nd nucleotide downstream of the m7GpppN), cap3 (additional methylation of the ribose of the 3rd nucleotide downstream of the m7GpppN), cap4 (additional methylation of the ribose of the 4th nucleotide downstream of the m7GpppN), ARCA (antireverse cap analogue), modified ARCA (e.g. phosphothioate modified ARCA), inosine, N1 -methylguanosine, 2’-fluoro-guanosine, 7-deaza-guanosine, 8-oxo-guanosine, 2-amino-guanosine, LNA- guanosine, and 2-azido-guanosine.Suitably, a 5’-cap (capO or cap1) structure may be formed in chemical RNA synthesis or in RNA in vitro transcription (co-transcriptional capping) using cap analogues.The term “cap analogue” refers to a non-polymerizable di-nucleotide or tri-nucleotide that has cap functionality in that it facilitates translation or localization, and / or prevents degradation of an RNA molecule when incorporated at the 5’-end of the nucleic acid molecule. Non-polymerizable means that the cap analogue will be incorporated only at the 5’-terminus because it does not have a 5’ triphosphate and therefore cannot be extended in the 3’-direction by a template-dependent polymerase, particularly, by template-dependent RNA polymerase.In embodiments, a cap1 structure is generated using a cap analogue as disclosed in WO2017053297, WO2017066793, WO2017066781 , WO2017066791 , WO2017066789, WO2017066782, WO2018075827, WO2017066797, and W02023007019. Preferably, cap structures derivable from the structure disclosed in claim 1 -5 of WO2017053297 may be suitably used to co-transcriptionally generate a cap1. Further, any cap structures as defined in claim 1 to claim 37 of W02023007019 may be suitably used to generate a cap1 structure.In preferred embodiments, the 5’-cap structure may suitably be added co-transcriptionally using trinucleotide cap analogue as defined herein, preferably in an RNA in vitro transcription reaction as defined herein.In particularly preferred embodiments, the artificial nucleic acid is an RNA that comprises a cap1 structure or a modified cap1 structure.In preferred embodiments, the cap1 structure is formed via co-transcriptional capping using tri-nucleotide cap analogues m7G(5’)ppp(5’)(2’OMeA)pG or m7G(5’)ppp(5’)(2’OMeG)pG. A particularly preferred cap1 analogue in that context is m7G(5’)ppp(5’)(2’OMeA)pG.In other preferred embodiments, the cap1 structure is a modified cap1 structure and is formed using co- transcriptional capping using tri-nucleotide cap analogue 3’0Me-m7G(5’)ppp(5’)(2’0MeA)pG.In other embodiments, the 5’-cap structure is formed via enzymatic capping using capping enzymes (e.g. vaccinia virus capping enzymes and / or cap-dependent 2’-0 methyltransferases) to generate capO, cap1 or cap2 structures. In that context, the 5’-cap structure (capO or cap1) may be added using immobilized capping enzymes and / or cap-dependent 2’-0 methyltransferases using methods and means disclosed in WO2016193226.In preferred embodiments, about 70%, 75%, 80%, 85%, 90%, 95% of the RNA comprises a cap structure, preferably a cap1 structure, as determined by a capping assay. For determining the presence or absence of a cap structure, capping assays as described in W02015101416, in particular, as described in claims 27 to 46 of W02015101416 can be used.Further RNA features:In various preferred embodiments, the artificial nucleic acid is an RNA that provides at least one coding sequence encoding the combination of tumour antigens as defined herein.Suitable elements that the RNA of the invention preferably comprises are for example a 5’-cap structure as defined herein, a 5’-UTR element as defined herein, a 3’-UTR element as defined herein, a hSL as defined herein, a poly(A) sequence as defined herein, and optional chemical modifications as defined herein.In preferred embodiments, the RNA is preferably an in vitro transcribed RNA (e.g. an in vitro transcribed mRNA).In some embodiments, the nucleotide mixture for RNA in vitro transcription comprises modified nucleotides as defined herein. In that context, preferred modified nucleotides may be selected from pseudouridine (qj) or N1 -methylpseudouridine (m1 qj). Suitably, uracil nucleotides in the nucleotide mixture are replaced (either partially or completely) by pseudouridine (qj) and / or N1 -methylpseudouridine (m1 qj) to obtain a modified RNA (e.g. a modified mRNA).In other embodiments, the nucleotide mixture for RNA in vitro transcription does not comprise modified nucleotides as defined herein. In embodiments, the nucleotide mixture used for RNA in vitro transcription does only comprise G, C, A and U nucleotides, and, optionally, a cap analogue as defined herein, to obtain a non-modified RNA (e.g. a non-modified mRNA).In preferred embodiments, the nucleotide mixture (i.e. the fraction of each nucleotide in the mixture) used for RNA in vitro transcription reactions is optimized for the given RNA sequence, preferably as described WO2015188933. Accordingly, in preferred embodiments, the nucleic acid of the invention is an in vitro transcribed RNA, preferably wherein RNA in vitro transcription has been performed in the presence of a sequence optimized nucleotide mixture.In the context of the invention (e.g. for RNA-based medicaments), it may be required to provide GMP-grade RNA. In preferred embodiments, RNA production is performed under current good manufacturing practice (GMP), implementing various quality control steps on DNA and RNA level, preferably quality control steps selected from methods described in W02016180430. In preferred embodiments, the RNA is a GMP-grade RNA, particularly a GMP-grade mRNA.In preferred embodiments, the artificial nucleic acid is a purified RNA, preferably a purified mRNA. Suitably, the RNA of the invention has been purified by at least one step of purification.The term “purified RNA” or “purified mRNA” as used herein has to be understood as RNA which has a higher purity after certain purification steps than the starting material (e.g. in vitro transcribed RNA). Typical impurities that are essentially not present in purified RNA comprise peptides or proteins (e.g. enzymes derived from DNA dependent RNA in vitro transcription, e.g. RNA polymerases, RNases, pyrophosphatase, restriction endonuclease, DNase), spermidine, BSA, abortive RNA sequences, RNA fragments (short double stranded RNA (dsRNA)), free nucleotides (modified nucleotides, conventional NTPs, cap analogue), template DNA fragments, buffer components (HEPES, TRIS, MgCh) etc. Other potential impurities that may be derived from e.g. fermentation procedures comprise bacterial impurities (bioburden, bacterial DNA) or impurities derived from purification procedures (organic solvents etc.). Accordingly, it is desirable in this regard for the “degree of RNA purity” to be as close as possible to 100%. Accordingly, “purified RNA” as used herein has a degree of purity of more than 75%, 80%, 85%, very particularly 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98% and most favourably 99% or more. The degree of purity is e.g. determined by an analytical HPLC, wherein the percentages provided above correspond to the ratio between the area of the peak for the target RNA and the total area of all peaks including the peaks representing the by-products. Alternatively, the degree of purity is e.g. determined by an analytical agarose gel electrophoresis or capillary gel electrophoresis.In preferred embodiments, the RNA is a purified RNA, wherein the RNA has been purified by at least one step of (RP)-HPLC, AEX, size exclusion chromatography (SEC), hydroxyapatite chromatography,tangential flow filtration (TFF), filtration, precipitation, core-bead flow through chromatography, oligo(dT) purification, cellulose-based purification, or any combination thereof.Preferably, the RNA has been purified using RP-HPLC (preferably as described in W02008077592) and / or TFF (preferably as described in WO2016193206) and / or oligo d(T) purification (preferably as described in WO2016180430) to e.g. to remove dsRNA, non-capped RNA and / or RNA fragments.In some embodiments, the RNA has been purified by a step of 5’ dephosphorylation of linear RNA, DNA digestion, protein digestion, and / or dsRNA digestion.According to preferred embodiments, the purified RNA has a purity level of at least about 70%, 75%, 80%, 85%, 90%, or 95%, preferably more than 95%. Suitably, the degree of purity is determined by analytical HPLC.In embodiments, the RNA has a certain RNA integrity. The term “RNA integrity” generally describes whether the complete nucleic acid sequence or RNA sequence is present. Low RNA integrity could be due to, amongst others, RNA degradation, RNA cleavage, incorrect or incomplete chemical synthesis of the RNA, incorrect base pairing, integration of modified nucleotides or the modification of already integrated nucleotides, lack of capping or incomplete capping, lack of polyadenylation or incomplete polyadenylation, or incomplete RNA in vitro transcription. RNA is a fragile molecule that can easily degrade, which may be caused e.g. by temperature, ribonucleases, pH or other factors (e.g. nucleophilic attacks, hydrolysis etc.), which may reduce the RNA integrity and, consequently, its functionality. The integrity of the RNA can be determined by RP-HPLC and may be based on determining the peak area (or “area under the peak”) of the expected full-length RNA (the RNA with the correct RNA length) in a chromatogram.In embodiments, the at least one nucleic acid, preferably the RNA, has an integrity ranging from about 40% to about 100%. In embodiments, the nucleic acid of the invention, preferably the RNA has an integrity of at least 50%, at least 60%, at least 70%, at least 80%, or at least 90%.In preferred embodiments, the artificial nucleic acid, preferably the RNA is suitable for use in treatment or prevention of a disease, disorder or condition, preferably a tumour or cancer disease, disorder, or condition or any disease, disorder, or condition related to tumour or cancer. The term “cancer” according to the disclosure also comprises cancer metastases.Preferred nucleic acid constructs:In the following, preferred nucleic acid constructs, in particular preferred RNA constructs of the invention are provided and described in detail. Notably, said features defining preferred nucleic acid constructs, in particular preferred RNA constructs may be applied to any nucleic acid in any aspect of the invention (e.g. artificial nucleic acid set, pharmaceutical composition, combination, kit, medical uses).In various embodiments, the artificial nucleic acid comprises at least the following elements:A) a 5’-cap structure, preferably as specified herein;B) at least one cds encoding at least one peptide or protein as defined herein;C) a 5 -UTR element and / or a 3 -UTR element, preferably as specified herein;D) at least one poly(A) sequence, preferably as specified herein.In preferred embodiments, the artificial nucleic acid, preferably the RNA, comprises the following sequence elements preferably in 5’- to 3’-direction:A) a 5’-cap structure, preferably a cap1 structure;B) a 5’-UTR element, preferably selected or derived from a 5’-UTR element of a HSD17B4 gene;C) a coding sequence encoding at least one peptide or protein as defined herein;D) a 3 -UTR element, preferably selected or derived from a 3’-UTR element of a PSMB3 gene;E) optionally, a histone stem-loop; andF) a poly(A) sequence, preferably comprising about 100 A nucleotides.In more preferred embodiments, the artificial nucleic acid, preferably the RNA, comprises the following sequence elements in 5’- to 3’-direction:A) a 5’-cap structure, preferably a cap1 structure;B) a 5 -UTR element, preferably selected or derived from a 5’-UTR element of a HSD17B4 gene that preferably comprises or consists of a nucleic acid sequence being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 13 or 65, or a fragment or a variant of any of these;C) a coding sequence that comprises a nucleic acid sequence preferably encoding an amino acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of the amino acid sequences SEQ ID NOs: 156-163, 172-179, or 180-187, or an immunogenic fragment or variant of any of these, more preferably encoding an amino acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of the amino acid sequences SEQ ID NOs: 157, 163, 173, 179, 181 , or 187, or an immunogenic fragment or variant of any of these;D) a 3 -UTR element, preferably selected or derived from a 3’-UTR element of a PSMB3 gene that preferably comprises or consists of a nucleic acid sequence being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 67, 113, 115, 117, 119, 121 , or 123, or a fragment or a variant of any of these;E) optionally, a histone stem-loop; andF) a poly(A) sequence, preferably comprising about 100 A nucleotides.In particularly preferred embodiments, the artificial nucleic acid, preferably the RNA, comprises the following sequence elements in 5’- to 3’-direction:A) a 5’-cap structure, preferably a cap1 structure;B) a 5 -UTR element, preferably selected or derived from a 5’-UTR element of a HSD17B4 gene that preferably comprises or consists of a nucleic acid sequence being identical or at least 70%, 80%, 85%,86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 13, or 65, or a fragment or a variant of any of these;C) a coding sequence preferably comprising or consisting of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of the nucleic acid sequences SEQ ID NOs: 240-247, 256-263, or 264- 271 , or a fragment or variant of any of these, more preferably comprising or consisting of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of the nucleic acid sequences SEQ ID NOs: 241 , 247, 257, 263, 265, or 271 , or a fragment or variant of any of these;D) a 3 -UTR element, preferably selected or derived from a 3’-UTR element of a PSMB3 gene that preferably comprises or consists of a nucleic acid sequence being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 67, 113, 115, 117, 119, 121 , or 123, or a fragment or a variant of any of these;E) optionally, a histone stem-loop, preferably comprising or consisting of a nucleic acid sequence identical or at least 80% identical to SEQ ID NO: 4, or a fragment or variant of any of these; andF) a poly(A) sequence, preferably comprising about 100 A nucleotides.Table 1 provides an overview of the amino acid and nucleic acid sequences regarding the TAAs, antigenic peptides, epitopes and fusion proteins of the invention. Column A provides a name for the sequence of the invention (e.g. TAA, antigenic peptide, epitope or fusion protein). Column B provides the amino acid SEQ ID NO of the respective amino acid sequence. Column C provides the SEQ ID NO of the wild type nucleic acid sequences (wt) for the full-length TAAs. Column D provides the SEQ ID NO of G / C optimized nucleic acid sequences (opt1) encoding the respective amino acid sequences. In column E, the corresponding SEQ ID NOs of different nucleic acid constructs, in particular RNA constructs, comprising G / C optimized coding sequences (opt1) as defined herein are provided (mRNA design HSD17B4 / PSMB3 hSL). Further information is provided under “feature key”, i.e. “source” (for nucleic acids or proteins) or “misc_feature” (for nucleic acids) or “REGION” (for proteins) of the respective SEQ ID NOs in the ST.26 sequence listing.Table 1: Overview of the amino acid and nucleic acid sequences regarding the TAAs, antigenic peptides, epitopes and fusion proteins of the inventionIn preferred embodiments, the artificial nucleic acid, preferably the RNA, comprises or consists of a nucleic acid sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%,94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 297-328, 694 or 695, or a fragment or variant of any of these sequences, preferably, wherein the RNA is preferably an mRNA that preferably has a 5’-cap structure.In preferred embodiments, the artificial nucleic acid, preferably the RNA, comprises or consists of a nucleic acid sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 297-328, or a fragment or variant of any of these sequences, wherein at least one, preferably all uracil nucleotides in said RNA sequences are replaced by pseudouridine (ip) nucleotides and / or N1 -methylpseudouridine (m1 qj) nucleotides, more preferably wherein all uracil nucleotides in said RNA sequences are m1 qj nucleotides.In particularly preferred embodiments, the artificial nucleic acid, preferably the RNA, comprises or consists of a nucleic acid sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 328, or a fragment or variant of any of these sequences, preferably, wherein the RNA is an mRNA that preferably has a 5’-cap structure.In even more particularly preferred embodiments, the mRNA is identical to SEQ ID NO: 328, wherein the mRNA preferably has a 5’-cap structure.Alternatively, in particularly preferred embodiments, the artificial nucleic acid, preferably the RNA, comprises or consists of a nucleic acid sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 694 or 695, or a fragment or variant of any of these sequences, preferably, wherein the RNA is an mRNA that preferably has a 5’-cap structure.2: Artificial nucleic acid set:In a second aspect, the invention provides an artificial nucleic acid set that encodes at least two polypeptides or proteins, the at least two polypeptide or protein comprising at least one antigenic peptide or protein from a suitable combination of tumour-associated antigens (TAA).It has to be noted that specific features and embodiments that are described in the context of the second aspect, that is the artificial nucleic acid set of the invention, are likewise applicable to any other aspect of the invention.In the context of the present invention, the term “artificial nucleic acid set” as used herein preferably means a combined occurrence of more than one distinct nucleic acid species. “Combined occurrence” means that the individual components of the artificial nucleic acid set may be provided as (physically) separate entities (e.g. as separate nucleic acid molecules, e.g. a DNA or RNA) or as a combined entity (e.g. as one nucleic acid molecule comprising all nucleic acid components of the set) or any combination thereof. Accordingly, in the context of the invention, an “artificial nucleic acid set” may comprise at least two nucleic acidsequences, optionally, 3, 4, 5, 6, 7, 8, 9, 10 or even more nucleic acid sequences. Said at least two nucleic acid sequences, optionally, 3, 4, 5, 6, 7, 8, 9, 10 or even more nucleic acid sequences, may be provided by one nucleic acid molecule, e.g., DNA or RNA, or may be provide by 2, 3, 4, 5, 6, 7, 8, 9, 10 or more separate nucleic acid molecules as further specified herein. In the context of the invention, the artificial nucleic acid set (that comprises at least two distinct nucleic acid sequences) collectively encodes the antigenic peptides or proteins from the TAAs as specified herein.In preferred embodiments, the artificial nucleic acid set comprises at least two distinct artificial nucleic acids, wherein each of the at least two distinct artificial nucleic acids comprises at least one coding sequence encoding at least one polypeptide or protein, wherein the at least two encoded polypeptides or proteins together comprise at least one antigenic peptide or protein from each of the TAAs- BCAN or a variant thereof,- NLGNX4 or a variant thereof,- PTPRZ1 or a variant thereof, and- BIRC5 or a variant thereof.In the context of the present invention, the term “at least two distinct artificial nucleic acids” as used herein preferably means that the at least two artificial nucleic acids are different to each other in sequence. The “at least two distinct artificial nucleic acids” may encode different components of the antigenic peptide or protein from the TAAs as specified herein.In preferred embodiments, the at least two encoded polypeptides or proteins together comprise the antigenic peptides or proteins that are encoded by the at least one coding sequence of the artificial nucleic acid as defined in the context of the first aspect.Accordingly, in other words, the artificial nucleic acid set collectively encodes the antigenic peptides or proteins as defined in the context of the first aspect.In preferred embodiments, the at least two encoded polypeptides or proteins comprise at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 antigenic peptides from at least one of the TAAs BCAN, NLGNX4, PTPRZ1 , BIRC5 or ELOVL2, or from a variant thereof.In preferred embodiments, the at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 antigenic peptides from the same TAA or variant thereof are comprised in the same encoded polypeptide or protein of the at least two encoded polypeptides or proteins.Accordingly, in other words, preferably all antigenic peptides from the same TAA or variant thereof are comprised in the same encoded polypeptide or protein of the at least two encoded polypeptides or proteins. In preferred embodiments, at least one, preferably each, of the at least two distinct artificial nucleic acids is characterized by any of the features as defined in the context of the first aspect, in particular, encoding the specified antigenic peptides from TAAs as defined in the context of the first aspect.Accordingly, in preferred embodiments, at least one, preferably each, of the at least two encoded polypeptides or protein comprises- at least one linker element as defined in the context of the first aspect, preferably a G4S linker;- at least one additional amino acid sequence selected from an IRSTepm or from a variant thereof as defined in the context of the first aspect, preferably CTLA4;- at least one additional amino acid sequence selected from a signal peptide or from a variant thereof as defined in the context of the first aspect; and / or- at least one amino acid sequence selected from a modulator element as defined in the context of the first aspect or eighth aspect, preferably a degron.Accordingly, in particularly preferred embodiments, the at least one, preferably each, of the at least two encoded polypeptides or protein comprises the following structure:• [Antigenic peptide of a TAA] - [G4S - antigenic peptide of a TAA]n and, optionally, [antigenic peptide of a marker antigen] and / or IRSTepm;• SP - [G4S - antigenic peptide of a TAA]n;• SP - [G4S - antigenic peptide of a TAA]n - [optionally antigenic peptide of a marker antigen];• SP - [G4S - antigenic peptide of a TAA]n - [optionally antigenic peptide of a marker antigen] - G4S- IRSTepm;• SP - [G4S - antigenic peptide of a TAA]n - [optionally antigenic peptide of a marker antigen] - G4S- IRSTepm; wherein each may optionally comprise a modulator element as defined herein, wherein n is selected from an integer ranging from 1 to 20, preferably 1 to 10, and wherein optionally the antigenic peptide of a marker antigen may comprise both a marker MHC-I epitope and a universal T helper epitope.Suitably, the artificial nucleic acids of the set are selected from RNA, preferably mRNA.Preferably, each of the distinct artificial nucleic acids of the set, preferably each RNA of the set, comprise the following sequence elements preferably in 5’- to 3’-direction:A) a 5’-cap structure, preferably a cap1 structure;B) a 5’-UTR element, preferably selected or derived from a 5’-UTR element of a HSD17B4 gene;C) a coding sequence encoding at least one polypeptide or protein as defined herein;D) a 3’-UTR element, preferably selected or derived from a 3’-UTR element of a PSMB3 gene;E) optionally, a histone stem-loop; andF) a poly(A) sequence, preferably comprising about 100 A nucleotides.In preferred embodiments, the at least two distinct artificial nucleic acids of the set, preferably the RNA of the set, are further characterized by any of the features and embodiments as described in the context of the first aspect, section “Nucleic acid sequence features and embodiments”.3: Composition:In a third aspect, the invention provides a composition comprising at least one artificial nucleic acid as defined in the first aspect, or at least one artificial nucleic acid set as defined in the second aspect.It has to be noted that specific features and embodiments that are described in the context of the third aspect, that is the composition of the invention, are likewise applicable to any other aspect of the invention.In various embodiments, the artificial nucleic acid or artificial nucleic acid set, preferably the at least one RNA, is formulated with at least one pharmaceutically acceptable carrier or pharmaceutically acceptable excipient. Accordingly, the composition is preferably a pharmaceutical composition.In preferred embodiments, the pharmaceutical composition comprises- an artificial nucleic acid as defined in in the context of the first aspect, or- an artificial nucleic acid set as defined in the context of the second aspect.In embodiments, the at least two artificial nucleic acids of the artificial nucleic acid set are co-formulated in one entity or formulated in separate entities.In various embodiments, the artificial nucleic acid or artificial nucleic acid set, preferably the at least one RNA, is complexed or associated with at least one further compound to obtain a formulated composition. A formulation in that context may have the function of a transfection agent. A formulation may also have the function of protecting the nucleic acid from degradation, e.g. to allow storage, shipment, etc..In embodiments, the at least one nucleic acid, preferably the at least one RNA, is formulated with at least one compound, e.g. peptides, proteins, lipids, polysaccharides, and / or polymers.In embodiments, the artificial nucleic acid or artificial nucleic acid set, preferably RNA, is formulated with at least one cationic (cationic or preferably ionizable) or polycationic compound (cationic or preferably ionizable). In preferred embodiments, the at least one nucleic acid, preferably the at least one RNA, is complexed or associated with or at least partially complexed or partially associated with one or more cationic (cationic or preferably ionizable) or polycationic compound.The term “cationic or polycationic compound” as used herein refers to a charged molecule, which is positively charged at a pH value ranging from about 1 to 9, at a pH value ranging from about 3 to 8, at a pH value ranging from about 4 to 8, at a pH value ranging from about 5 to 8, more preferably at a pH value ranging from about 6 to 8, even more preferably at a pH value ranging from about 7 to 8, most preferably at a physiological pH, e.g. ranging from about 7.2 to about 7.5. Accordingly, a cationic component, e.g. a cationic peptide, cationic protein, cationic polymer, cationic polysaccharide, cationic lipid may be any positively charged compound or polymer which is positively charged under physiological conditions. A “cationic or polycationic peptide or protein” may contain at least one positively charged amino acid, or morethan one positively charged amino acid, e.g. selected from Arg, His, Lys or Orn. Accordingly, “polycationic” components are also within the scope exhibiting more than one positive charge under the given conditions.In preferred embodiments, the at least one cationic or polycationic compound is selected from a cationic or polycationic polymer, a cationic or polycationic polysaccharide, a cationic or polycationic lipid, a cationic or polycationic protein, a cationic or polycationic peptide, or any combinations thereof. Preferably, the at least one cationic or polycationic compound is selected from a cationic or polycationic lipid.In particularly preferred embodiments, the artificial nucleic acid or artificial nucleic acid set, preferably RNA, is formulated in a lipid-based carrier.In the context of the invention, the term “lipid-based carrier” encompass a lipid-based delivery system for nucleic acid, preferably RNA, that comprise a lipid component. A lipid-based carrier may additionally comprise other components suitable for encapsulating / incorporating / complexing a nucleic acid including a cationic or polycationic polymer, a cationic or polycationic polysaccharide, a cationic or polycationic protein, a cationic or polycationic peptide, or any combinations thereof.A typical “lipid-based carrier” may be selected from liposomes, lipid nanoparticles (LNPs), lipoplexes, solid lipid nanoparticles, and / or nanoliposomes. The artificial nucleic acid of the composition (e.g. RNA) may completely or partially be incorporated or encapsulated in a lipid-based carrier, wherein the at least one nucleic acid may be located in the interior space of the lipid-based carrier, within the lipid layer / membrane of the lipid-based carrier, or associated with the exterior surface of the lipid-based carrier. The incorporation of nucleic acid such as RNA into lipid-based carriers may be referred to as “encapsulation”. A “lipid-based carrier” is not restricted to any particular morphology, and include any morphology generated when e.g., an aggregation reducing lipid and at least one further lipid are combined, e.g., in an aqueous environment in the presence of nucleic acid. For example, an LNP, a liposome, a lipid complex, a lipoplex and the like are within the scope of the term “lipid-based carrier”. Lipid-based carriers can be of different sizes such as, but not limited to, a multilamellar vesicle (MLV) which may be hundreds of nanometers in diameter and may contain a series of concentric bilayers separated by narrow aqueous compartments, a small unicellular vesicle (SUV) which may be smaller than 50nm in diameter, and a large unilamellar vesicle (LUV) which may be between 50nm and 500nm in diameter. Liposomes, a specific type of lipid-based carrier, are characterized as microscopic vesicles having an interior aqua space sequestered from an outer medium by a membrane of one or more bilayers. In a liposome, the at least one nucleic acid (e.g. RNA) is typically located in the interior aqueous space enveloped by some or the entire lipid portion of the liposome. Bilayer membranes of liposomes are typically formed by amphiphilic molecules, such as lipids of synthetic or natural origin that comprise spatially separated hydrophilic and hydrophobic domains. Lipid nanoparticles (LNPs), a specific type of lipid-based carrier, are characterized as microscopic lipid particles having a solid core or partially solid core. Typically, an LNP does not comprise an interior aqua space sequestered from an outer medium by a bilayer.In embodiments, the lipid-based carrier is selected from lipid nanoparticles, liposomes, lipoplexes, solid lipid nanoparticles, lipo-polyplexes, and / or nanoliposomes.In particularly preferred embodiments, the lipid-based carrier is a lipid nanoparticles (LNPs). In an LNP, the at least one nucleic acid (e.g. RNA) may be encapsulated or incorporated in the lipid portion of the LNP enveloped by some or the entire lipid portion of the LNP. An LNP may comprise any lipid capable of forming a particle to which the nucleic acid such as the RNA may be attached, or in which the nucleic acid such as the RNA may be encapsulated.In particularly preferred embodiments, the lipid nanoparticles (LNPs) encapsulate the nucleic acid.The term “encapsulated”, e.g. incorporated, complexed, encapsulated, partially encapsulated, associated, partially associated, refers to the essentially stable combination of nucleic acid such as RNA with one or more lipids into lipid-based carriers (e.g. larger complexes or assemblies) preferably without covalent binding of the nucleic acid. The lipid-based carriers (e.g. LNPs) - encapsulated nucleic acid (e.g. RNA) may be completely or partially located in the interior of the lipid-based carrier (e.g. the lipid portion and / or an interior space) and / or within the lipid layer / membrane of the lipid-based carriers. The encapsulation of nucleic acid such as RNA into lipid-based carriers (e.g. LNPs) is also referred to herein as “incorporation” as the nucleic acid is preferably contained within the interior of the lipid-based carriers. Without wishing to be bound to theory, the purpose of incorporating or encapsulating nucleic acid such as RNA into lipid-based carriers may be to protect the nucleic acid from an environment which may contain enzymes, chemicals, or conditions that degrade the nucleic acid, in particular the RNA. Moreover, incorporating nucleic acid such as RNA into lipid-based carriers may promote the uptake of the nucleic acid and their release from the endosomal compartment, and hence, may enhance the therapeutic effect of the nucleic acid, in particular the RNA, when administered to a cell or a subject.In preferred embodiments, the lipid-based carrier, preferably the LNP, comprises at least one or more lipids selected from at least one aggregation-reducing lipid, at least one cationic lipid or ionizable lipid, at least one neutral lipid or phospholipid, or at least one steroid or steroid analogue, or any combinations thereof.In preferred embodiments, the lipid-based carrier, preferably the LNP, comprises an (i) at least one aggregation-reducing lipid, (ii) at least one cationic lipid or ionizable lipid, (iii) at least one neutral lipid or phospholipid, (iv) and at least one steroid or steroid analogue.In particularly preferred embodiments, the lipid-based carrier, preferably the LNP, comprises (i) an aggregation-reducing lipid, (ii) a cationic lipid or ionizable lipid, (iii) two different neutral lipids or phospholipids, and (iv) a steroid or steroid analog.Aggregation reducing lipids / polymer conjugated lipidsIn preferred embodiments, the lipid-based carrier, preferably the LNP, comprise at least one aggregation reducing lipid or aggregation reducing moiety.The term “aggregation reducing moiety” refers to a molecule comprising a moiety suitable of reducing or preventing aggregation of the lipid-based carriers, preferably the LNPs. The term “aggregation reducing lipid” refers to a molecule comprising both a lipid portion and a moiety suitable of reducing or preventing aggregation of the lipid-based carriers. Under storage conditions or during formulation, the lipid-based carriers such as LNPs may undergo charge-induced aggregation, a condition which can be undesirable for the stability of the lipid-based carriers. Therefore, it can be desirable to include a compound or moiety which can reduce aggregation, e.g. by sterically stabilizing the lipid-based carriers. Such a steric stabilization may occur when a compound having a sterically bulky but uncharged moiety that shields or screens the charged portions of a lipid-based carriers from close approach to other lipid-based carriers in the composition. Stabilization of the lipid-based carriers, preferably the LNPs, may be achieved by including lipids which may comprise a lipid bearing a sterically bulky group which, after formation of the lipid-based carrier, is preferably located on the exterior of the lipid-based carrier. Suitable aggregation reducing groups may include hydrophilic groups, e.g. monosialoganglioside GM1 , polyamide oligomers (PAO), or certain polymers, such as poly(oxyalkylenes), e.g., poly(ethylene glycol) or polypropylene glycol).In preferred embodiments, the aggregation reducing lipid is selected from a polymer conjugated lipid.Lipids comprising a polymer as aggregation reducing group are herein referred to as “polymer conjugated lipid”.The term “polymer conjugated lipid” refers to a molecule comprising both a lipid portion and a polymer portion, wherein the polymer is suitable of reducing or preventing aggregation of lipid-based carriers comprising the nucleic acid. A polymer has to be understood as a substance or material consisting of very large molecules, or macromolecules, composed of many repeating subunits. A suitable polymer in the context of the invention may be a hydrophilic polymer. An example of a polymer conjugated lipid is a PEGylated or PEG-conjugated lipid.In embodiments, the polymer conjugated lipid is selected from a PEG-conjugated lipid or a PEG-free lipid.In preferred embodiments, the polymer conjugated lipid is a PEG-conjugated lipid (or PEGylated lipid, PEG lipid). In preferred embodiments, polymer conjugated lipid is selected or derived from DMG-PEG 2000, C10-PEG2K, Cer8-PEG2K, POZ-lipid, or ALC-0159.The average molecular weight of the PEG moiety in the PEG- conjugated lipid preferably ranges from about 500 to about 8,000 Daltons (e.g., from about 1 ,000 to about 4,000 Daltons). In one preferred embodiment, the average molecular weight of the PEG moiety is about 2,000 Daltons. In embodiments, the polymer conjugated lipid, e.g. the PEG-conjugated lipid, is selected or derived from 1 ,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (PEG2000 DMG or DMG-PEG 2000). In other embodiments, the polymer conjugated lipid, e.g. the PEG-conjugated lipid, is selected or derived from C10-PEG2K, or Cer8-PEG2K.In other embodiments, the polymer conjugated lipid, e.g. the PEG-conjugated lipid, is selected or derived from formula (IV) of WO2018078053, preferably selected from formula (IVa) of WO2018078053. In thatcontext, a PEG-conjugated lipid selected or derived from formula IVa may have the chemical term 2[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, also referred to as ALC-0159.In other preferred embodiments, the lipid-based carriers, preferably the LNPs, comprise an aggregation reducing lipid, wherein the aggregation reducing lipid is not a PEG-conjugated lipid. Accordingly, the aggregation reducing lipid may suitably be selected from a PEG-free lipid, e.g. a PEG-free polymer conjugated lipid. In preferred embodiments, the aggregation reducing lipid (or polymer conjugated lipid) is a PEG-free lipid that comprises a polymer different from PEG. In preferred embodiments, the lipid-based carriers, preferably the LNPs, do not comprise a PEG-conjugated lipid.A PEG-free lipid in the context of the invention may be selected or derived from a “POZ-lipid”. In preferred embodiments, the “POZ lipids” or respectively preferred polymer conjugated lipids are described in WO2023031394, the full disclosure herewith incorporated by reference. In particular, the disclosure relating to polymer conjugated lipids as shown in any one of claims 1 to 8 of WO2023031394 are incorporated by reference.In embodiments, the polymer conjugated lipid is a PEG-free lipid selected from a POZ-lipid.Accordingly, in embodiments, the polymer conjugated lipid is a “POZ-lipid”, which preferably is defined as a compound according to formula (POZ): [H] - [linker] - [M], wherein[H] is a homopolymer moiety comprising at least one polyoxazoline (POZ) monomer unitwherein R is C1-9 alkyl or C2-9 alkenyl, preferably C1 , and n has a mean value ranging from 2 to 200, preferably from 20 to 100, more preferably from 24 to 26 or 45 to 50; [linker] is an optional linker group; [M] is a lipid moiety.In an embodiment in that context, [H] is a heteropolymer moiety or homopolymer moiety comprising multiple monomer units selected from the group consisting of poly(2-methyl-2-oxazoline) (PMOZ), poly(2-ethyl-2- oxazoline) (PEOZ), poly(2-propyl-2-oxazoline) (PPOZ), poly(2-butyl-2-oxazoline) (PBOZ), poly(2-isopropyl- 2-oxazoline) (PIPOZ), poly(2-methoxymethyl-2-oxazoline) (PMeOMeOx), and poly(2-dimethylamino-2- oxazoline) (PDMAOx), preferably wherein [H] is a homopolymer moiety comprising multiple PMOZ or PEOZ monomer units, more preferably wherein [H] comprises or preferably consists of multiple PMOZ monomer units, wherein (i) n has a mean value ranging from 2 to 200, preferably from 20 to 100, more preferably from 24 to 26 or 45 to 50 or wherein (ii) n is selected such that the [H] moiety has an average molecular weight of 1 .5 to 22 kDa, more preferably of 2 to 19 kDa, even more preferably of about 7.5 kDa or of about 15 kDa, preferably from 1 to 15 kDa, more preferably of 2 to 12.5 kDa, even more preferably of about 5 kDa or of about 10 kDa. In another embodiment in the context of POZ-lipids, [H] is a heteropolymer moiety or homopolymer moiety comprising multiple monomer units selected from the group consisting of PmeOx,PETOx, PnPrOx, PcPrOx, PiPrOx, PsecBuOx, PiBuOx, PnBuOx, PPentOx, PheptOx, PNOx, PPheOx, PButEnOx, PPynOx, PDecEnOx, PiPrEnOx, and PIPOx. In yet another embodiment in that context, the [H] from the polymer conjugated lipid according to formula (POZ) is selected from the group consisting of poly(2-methoxymethyl-2-oxazoline) (PMeOMeOx) and poly(2-dimethylamino-2-oxazoline) (PDMAOx).In one embodiment in that context, the lipid moiety [M] as shown in formula (POZ) comprises at least one straight or branched, saturated or unsaturated alkyl chain containing from 6 to 30 carbon atoms, preferably wherein the lipid moiety [M] comprises at least one straight or branched saturated alkyl chain, wherein the alkyl chain is optionally interrupted by one or more biodegradable group(s) and / or optionally comprises one terminal biodegradable group, wherein the biodegradable group is selected from the group consisting of but not limited to a pH-sensitive moiety, a zwitterionic linker, non-ester containing linker moieties and ester- containing linker moieties ( — C(O)O — or — OC(O) — ), amido ( — C(O)NH — ), disulfide ( — S — S — ), carbonyl ( — C(O) — ), ether ( — O — ), thioether ( — S — ), oxime (e.g., — C(H)=N — O — or — O — N=C(H) — ), carbamate (— NHC(O)O— ), urea (— NHC(O)NH— ), succinyl (— (O)CCH2CH2C(O)— ), succinamidyl (— NHC(O)CH2CH2C(O)NH— ), — C(R5)=N— , — N=C(R5)— , — C(R5)=N— O— , — O— N=C(R5)— , — O— C(O)O— , — C(O)N(R5), — N(R5)C(O)— , — C(S)(NR5)— , (NR5)C(S)— , — N(R5)C(O)N(R5)— , — C(O)S— , — SC(O)— , — C(S)O— , — OC(S)— , — OSi(R5)2O— , — C(O)(CR3R4)C(O)O— , or —OC(O)(CR3R4)C(O) — , carbonate ( — OC(O)O — ), succinoyl, phosphate esters ( — O — (O)POH — O — ), cyclic compound, heterocyclic compound, piperidine, pyrazine, pyridine, piperazine, and sulfonate esters, as well as combinations thereof, wherein R3, R4 and R5 are, independently H or alkyl (e.g. C1 -C4 alkyl). In another embodiment in that context, the lipid moiety [M] comprises at least one straight or branched, saturated or unsaturated alkyl chain comprising 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, or 30 carbon atoms, preferably in the range of 10 to 20 carbon atoms, more preferably in the range of 12 to 18 carbon atoms, even more preferably 14, 16 or 18 carbon atoms, even more preferably 16 or 18 carbon atoms, most preferably 14 carbon atoms, wherein all selections are independent of one another.In one embodiment in that context, the linker group [linker] as shown in formula (POZ) is selected from the group consisting of but not limited to a pH-sensitive moiety, a zwitterionic linker, non-ester containing linker moieties and ester-containing linker moieties ( — C(O)O — or — OC(O) — ), amido ( — C(O)NH — ), disulfide ( — S — S — ), carbonyl ( — C(O) — ), ether ( — O — ), thioether ( — S — ), oxime (e.g., — C(H)=N — O — or — O — N=C(H)— ), carbamate (— NHC(O)O— ), urea (— NHC(O)NH— ), succinyl (— (O)CCH2CH2C(O)— ), succinamidyl (— NHC(O)CH2CH2C(O)NH— ), — C(R5)=N— , — N=C(R5)— , — C(R5)=N— O— , — O— N=C(R5)— , — O— C(O)O— , — C(O)N(R5), — N(R5)C(O)— , — C(S)(NR5)— , (NR5)C(S)— , — N(R5)C(O)N(R5)— , — C(O)S— , — SC(O)— , — C(S)O— , — OC(S)— , — OSi(R5)2O— , —C(O)(CR3R4)C(O)O — , or — OC(O)(CR3R4)C(O) — , carbonate ( — OC(O)O — ), succinoyl, phosphate esters ( — O — (O)POH — O — ), and sulfonate esters, as well as combinations thereof, wherein R3, R4 and R5 are, independently H or alkyl (e.g. C1 -C4 alkyl).In preferred embodiment in the context of POZ-lipids, the polymer conjugated lipid is selected or derived from PMOZ 1 , PMOZ 2, PMOZ 3, PMOZ 4, or PMOZ 5 of WO2023031394. In a particularly preferredembodiment in the context of POZ-lipids, the polymer conjugated lipid is selected or derived from PMOZ4 of WO2023031394.In particularly preferred embodiments, the at least one aggregation-reducing lipid is selected or derived from PMOZ4 according to or derived from the following formula:(PMOZ4)In another preferred embodiment in that context, the linker group [linker] comprises preferably an amide linker moiety. In a further preferred embodiment in that context, the linker group [linker] comprises preferably an ester linker moiety. In a further preferred embodiment in that context t, the linker group [linker] comprises preferably a succinate linker moiety. In another preferred embodiment in that context, the linker group [linker] comprises both an ester linker and an amid linker moiety. In another preferred embodiment, the linker group [linker] comprises both an ester linker, an amine linker and an amid linker moiety.In embodiments, the at least one aggregation-reducing lipid, preferably the polymer conjugated lipid, is selected or derived from ALC-0159, DMG-PEG 2000, C10-PEG2K, Cer8-PEG2K, or a POZ-lipid (as defined herein).In preferred embodiments, the at least one aggregation-reducing lipid, preferably the polymer conjugated lipid, is selected from DMG-PEG 2000, C10-PEG2K, Cer8-PEG2K, or a POZ-lipid (as defined herein).In particularly preferred embodiments, the aggregation-reducing lipid is selected from a PMOZ-lipid as defined herein. In preferred embodiments, the POZ-lipid is selected from a PMOZ4 lipid according to or derived from formula PMOZ4.In some embodiments, the lipid-based carrier, preferably the LNP, includes less than about 3, 2, or 1 mole percent of aggregation reducing lipid, based on the total moles of lipid in the lipid-based carrier. In further embodiments, lipid-based carriers, preferably the LNPs, comprise from about 0.1 % to about 10% of the aggregation reducing lipid on a molar basis, e.g., about 0.5 to about 10%, about 0.5 to about 5% on a molar basis (based on 100% total moles of lipids in the lipid-based carrier). In other embodiments, lipid-based carriers, preferably the LNPs, comprise from about 1.0% to about 2.0% of the aggregation reducing lipid on a molar basis (based on 100% total moles of lipids in the lipid-based carrier). In other embodiments, lipid-based carriers, preferably the LNPs, comprise about 2.5%, 3%, 3.5%, 4%, 4.5% or 5% of the aggregation reducing lipid on a molar basis (based on 100% total moles of lipids in the lipid-based carrier). In various embodiments, the molar ratio of the cationic lipid to the aggregation reducing lipid ranges from about 100:1 to about 25:1 .Cationic lipidsIn preferred embodiments, the lipid-based carrier, preferably the LNP, comprises at least one cationic or ionizable lipid.The cationic or ionizable lipid may be cationisable or ionizable, i.e. it becomes protonated as the pH is lowered below the pK of the ionizable group of the lipid, but is progressively more neutral at higher pH values. At pH values below the pK, the lipid is then able to associate with negatively charged nucleic acids. In certain embodiments, the cationic lipid comprises a zwitterionic lipid that assumes a positive charge on pH decrease.In preferred embodiments, the cationic or ionizable lipid preferably carries a net positive charge at physiological pH. Preferably the cationic or ionizable lipid comprises a quaternary nitrogen group or tertiary nitrogen group, most preferably a tertiary nitrogen group. Accordingly, in preferred embodiments, the at least one cationic or ionizable lipid may be selected from an amino lipid.Preferably, the at least one cationic lipid or ionizable lipid is selected from an amino lipid, preferably wherein the amino lipid comprises a tertiary amine group.In further embodiments, the at least one cationic lipid or ionizable lipid is selected from lipids as defined in formula I of paragraph

[0251] of WO2021222801 or a lipid selected from the disclosure of paragraphs

[0260] or

[0261] of WO2021222801. In other embodiments, the cationic lipid or ionizable lipid is selected from the group consisting of ATX-001 to ATX-132 as disclosed in claim 90 of WO2021183563, preferably ATX-0126. The disclosure of WO2021222801 and WO2021183563, especially aforementioned lipids, are incorporated herewith by reference.In preferred embodiments, the at least one cationic or ionizable lipid is a lipid selected or derived from formula (111-1)preferably, wherein one of L1 or L2 is -O(C=O)-, -<C=O)O-, -C(=O)-, -O-, -S(O)x-, -S-S-, -C(=O)S-, SC(=O)- , -NRaC(=O)-, -C(=O)NRa-, -NRaC(=O)NRa-, -OC(=O)NRa- or -NRaC(=O)O-, and the other of L1 or L2 is -O(C=O)-, -(C=O)O-, -C(=O)-, -O-, -S(O)x-, -S S-, -C(=O)S-, SC(=O)-, -NRaC(=O)-, -C(=O)NRa-, - NRaC(=O)NRa-, -OC(=O)NRa- or -NRaC(=O)O- or a direct bond; G1 and G2 are each independently unsubstituted C1-C12 alkylene or C1 -C12 alkenylene; G3 is C1-C24 alkylene, C1-C24 alkenylene, C3-C8 cycloalkylene, C3-C8 cycloalkenylene; Ra is H or C1-C12 alkyl; R1 and R2 are each independently C6-C24 alkyl or C6-C24 alkenyl; R3 is H, OR5, CN, C(=O)OR4, OC(=O)R4 or -NR5C(=O)R4; R4 is C1-C12 alkyl; R5 is H or C1 -C6 alkyl; and x is 0, 1 or 2.In some embodiments, cationic or ionizable lipids may be selected from the lipids disclosed in W02018078053 (i.e. lipids derived from formula I, II, and III of WO2018078053, or lipids as specified in claims 1 to 12), the disclosure of WO2018078053 hereby incorporated by reference in its entirety. In that context, lipids disclosed in Table 7 of WO2018078053 (e.g. lipids derived from formula 1-1 to 1-41) and lipids disclosed in Table 8 of WO2018078053 (e.g. lipids derived from formula 11-1 to II-36) may be suitably used in the context of the invention. Accordingly, formula 1-1 to formula 1-41 and formula 11-1 to formula II-36 of WO2018078053, and the specific disclosure relating thereto, are herewith incorporated by reference.In embodiments, the lipid-based carrier comprise at least one cationic lipid selected or derived from structures 111-1 to HI-36 of Table 9 of published PCT patent application WO2018078053. Accordingly, formula 111-1 to HI-36 of WO2018078053, and the specific disclosure relating thereto, are herewith incorporated by reference.In embodiments, the lipid-based carrier comprise a cationic lipid selected or derived from formula I II -3 of published PCT patent application WO2018078053. A preferred lipid of said formula HI-3 has the chemical term ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), also referred to as ALC-0315, i.e. CAS Number 2036272-55-4.Further suitable cationic lipids may be selected or derived from cationic lipids according to PCT claims 1 to 14 of published patent application WO2021123332, or Table 1 of WO2021123332, the disclosure relating to claims 1 to 14 or Table 1 of WO2021123332 herewith incorporated by reference. Accordingly, suitable cationic lipids may be selected or derived from cationic lipids according to Compound 1 to Compound 27 (C1-C27) of Table 1 of WO2021 123332.In preferred embodiments, the lipid-based carrier comprises a cationic lipid selected or derived from (COATSOME®SS-EC) SS-33 / 4PE-15 (see C23 in Table 1 of WO2021123332).In other preferred embodiments, the lipid-based carrier comprises a cationic lipid selected or derived from HEXA-C5DE-PipSS (see C2 in Table 1 of WO2021123332).In particularly preferred embodiments, the lipid-based carrier comprises a cationic lipid selected or derived from compound C26 as disclosed in Table 1 of WO2021 123332, or according to or derived from the following formula:In other embodiments, the lipid-based carrier comprises a cationic lipid selected or derived from 9- Heptadecanyl 8-{(2-hydroxyethyl)[6-oxo-6-(undecyloxy)hexyl]amino}octanoate, also referred to as SM- 102. Other preferred lipid-based carriers of comprise a squaramide ionizable amino lipid, more preferably a cationic lipid selected from the group consisting of formulas (M1) and (M2):(M1); w) are defined in claims 1 to 13 of US10392341 B2; US10392341 B2 being incorporated herein in its entirety.Accordingly, in embodiments, the lipid-based carrier, preferably the LNP, comprises a cationic lipid selected or derived from ALC-0315, SM-102, SS-33 / 4PE-15, HEXA-C5DE-PipSS, or compound C26. In preferred embodiments, the lipid-based carrier, preferably the LNP, comprises at least one cationic lipid selected from compound C26, SS-33 / 4PE-15, HEXA-C5DE-PipSS, or SM-102.In particularly preferred embodiments, the at least one cationic lipid is selected from compound C26.In some embodiments, the lipid-based carrier of the invention comprise two or more (different) cationic lipids as defined herein.In certain embodiments, the cationic lipid as defined herein is present in the lipid-based carrier in an amount from about 30mol% to about 95mol%, relative to the total lipid content of the lipid-based carriers. If more than one cationic lipid is incorporated within the lipid-based carriers, such percentages apply to the combined cationic lipids.In embodiments, the cationic lipid as defined herein is present in the lipid-based carrier in an amount from about 30 to about 95 mole percent, relative to the total lipid content of the lipid-based carriers. If more than one cationic lipid is incorporated within the lipid-based carriers, such percentages apply to the combined cationic lipids.In embodiments, the cationic lipid is present in the lipid-based carrier in an amount from about 20 to about 75 mole percent. In one embodiment, the cationic lipid is present in the lipid-based carriers in an amount from about 40 to about 60 mole percent. In embodiments, the cationic lipid is present in the lipid-based carriers in an amount from about 55 to about 65 mole percent. These values are based upon 100% total moles of lipid in the lipid-based carriers.In some embodiments, the ratio of cationic lipid to nucleic acid, preferably to RNA is from about 3 to about 15, such as from about 5 to about 13 or from about 7 to about 11 .Neutral LipidsIn preferred embodiments, the lipid-based carrier, preferably the LNP, comprises at least one neutral lipid or phospholipid.The term “neutral lipid” refers to any one of a number of lipid species that exist in either an uncharged or neutral zwitterionic form at physiological pH. Suitable neutral lipids include diacylphosphatidylcholines, diacylphosphatidylethanolamines, ceramides, sphingomyelins, dihydrosphingomyelins, cephalins, and cerebrosides. The selection of neutral lipids for use in the particles described herein is generally guided by consideration of, e.g., lipid particle size and stability of the lipid particle in the bloodstream. Preferably, the neutral lipid is a lipid having two acyl groups (e.g., diacylphosphatidylcholine and diacylphosphatidylethanolamine). In one embodiment, the neutral lipids contain saturated fatty acids with carbon chain lengths in the range of C10 to C20. In other embodiments, neutral lipids with mono or diunsaturated fatty acids with carbon chain lengths in the range of C10 to C20 may be used. Additionally, neutral lipids having mixtures of saturated and unsaturated fatty acid chains can be used.In embodiments, the lipid-based carrier, preferably the LNP, comprises one or more neutral lipids, wherein the neutral lipid is selected from DOPC, DPPC, DOPG, DPPG, DOPE, POPC, POPE, DOPE-mal, DPPE, DMPE, DSPE, 16-O-monomethyl PE, 16-O-dimethyl PE, 18-1 -trans PE, SOPE, transDOPE, or mixtures thereof. In some embodiments, the neutral lipid of the lipid-based carriers is selected or derived from 1 ,2-diheptanoyl-sn-glycero-3-phosphocholine (DHPC). In preferred embodiments, the neutral lipid of the lipid- based carriers is selected or derived from 1 ,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (DPhyPE). In other preferred embodiments, the neutral lipid of the lipid-based carriers is selected or derived from phosphatidylserine, preferably DPhyPS (1 ,2-diphytanoyl-sn-glycero-3-phospho-L-serine). In other embodiments, the neutral lipid of the lipid-based carriers is selected or derived from 1 ,2-distearoyl-sn- glycero-3-phosphocholine (DSPC).Accordingly, in preferred embodiments, the at least one neutral lipid is selected or derived from DSPC, DHPC, DPhyPE, or DPhyPS. In more preferred embodiments, the at least one neutral lipid is selected or derived from DPhyPE and / or DphyPS. In other preferred embodiments, one neutral lipid or phospholipid is selected from DSPC, DHPC, DPhyPE and one neutral lipid or phospholipid is selected from DPhyPS.In particularly preferred embodiments, the lipid-based carrier, preferably the LNP, comprises DPhyPE and DPhyPS.In various embodiments, the molar ratio of the cationic lipid to the neutral lipid in the lipid-based carriers ranges from about 2:1 to about 8:1 .The neutral lipid is preferably from about 5mol% to about 90mol%, about 5mol% to about 10mol%, of the total lipid present in the lipid-based carrier. In one embodiment, the lipid-based carrier includes from about 0% to about 15% or 45% on a molar basis of neutral lipid.Steroids, steroid analogs or sterolsIn preferred embodiments, the lipid-based carrier, preferably the LNP, comprises a steroid, steroid analog or sterol.In preferred embodiments, the steroid or steroid analog is selected or derived from cholesterol or cholesteryl hemisuccinate (CHEMS), preferably cholesterol.In other embodiments, the lipid-based carrier comprise a steroid, steroid analog or sterol derived from a phytosterol (e.g., a sitosterol, such as beta-sitosterol), preferably from a compound having the structure of Formula I as disclosed in claim 1 of W02020061332; the disclosure of W02020061332, especially the disclosure of Formula I and phytosterols being incorporated herewith by reference. In a further embodiment, the steroid is an imidazole cholesterol ester or “ICE” as disclosed in paragraphs

[0320] and

[0339] -

[0340] of WO2019226925A1 ; WO2019226925A1 being incorporated herein by reference in its entirety.In particularly preferred embodiments, the lipid-based carrier comprise a sterol, preferably cholesterol.The molar ratio of the cationic lipid to sterol, preferably cholesterol, in the lipid-based carriers may be in the range from about 2:1 to about 1 :1 . In some embodiments, the lipid-based carrier comprises about 10mol% to about 60mol% or about 25mol% to about 50mol% sterol, preferably sterol, preferably about 35mol% toabout 45mol% sterol, more preferably about 40mol% cholesterol (based on 100% total moles of lipids in the lipid-based carrier).In embodiments, the lipid-based carrier, preferably the LNP, comprising the nucleic acid, preferably theRNA, comprise(i) at least one cationic lipid or ionizable lipid, preferably as defined herein;(ii) at least one or two (e.g. two different) neutral lipids or phospholipids, preferably as defined herein;(iii) at least one steroid or steroid analogue, preferably as defined herein; and(iv) at least one aggregation reducing lipid, preferably as defined herein.In preferred embodiments, the lipid-based carrier, preferably the LNP, comprising the nucleic acid, preferably the RNA, comprise(i) at least one cationic lipid selected or derived from C26, SS-33 / 4PE-15, HEXA-C5DE-PipSS, SM-102;(ii) at least one or two (e.g. two different) neutral lipids selected or derived from DSPC, DHPC, DPhyPE, DPhyPS;(iii) at least one steroid or steroid analog selected or derived from cholesterol; and(iv) at least one aggregation reducing lipid selected or derived from DMG-PEG 2000, C10-PEG2K, Cer8- PEG2K, or a POZ lipid (e.g. PMOZ 4); wherein the lipid-based carriers preferably encapsulate the artificial nucleic acid or set.In particularly preferred embodiments, the lipid-based carrier, preferably the LNP, comprising nucleic acid, preferably the RNA, comprise(i) a cationic lipid selected from compound C26;(ii) a neutral lipid selected from DPhyPE and a neutral lipid selected from DPhyPS;(iii) a steroid or steroid analog selected from cholesterol; and(iv) an aggregation reducing lipid selected from a POZ-lipid, preferably from PMOZ 4; wherein the lipid- based carriers preferably encapsulate the artificial nucleic acid or set.In preferred embodiments, the cationic lipids (as defined herein), the neutral lipids (as defined herein), the steroid or steroid analogs (as defined herein), and / or the aggregation reducing lipids (as defined herein) may be combined at various relative ratios.In preferred embodiments, the lipid-based carrier, preferably the LNP, comprises (i) to (iv) in a molar ratio of about 20-60% cationic lipid or ionizable lipid, about 5-25% neutral lipid, about 25-55% steroid or steroid analogue, and about 0.5-15% aggregation reducing lipid e.g. polymer conjugated lipid, preferably wherein the lipid-based carriers encapsulate the at least one nucleic acid, preferably the at least one RNA.In more preferred embodiments, the lipid-based carrier, preferably the LNP, comprises (i) to (iv) in a molar ratio of about 45-55% cationic lipid or ionizable lipid, about 5-15% neutral lipid, about 35-45% steroid orsteroid analogue, and about 0.5-2.5% aggregation reducing lipid e.g. polymer conjugated lipid, preferably wherein the lipid-based carriers encapsulate the at least one nucleic acid, preferably the at least one RNA.In even more preferred embodiments, the lipid-based carrier, preferably the LNP, comprises (i) to (iv) in a molar ratio of about 47-51 % cationic lipid or ionizable lipid, about 8-12% neutral lipid, about 38-42% steroid or steroid analogue, and about 0.75-1.75% aggregation reducing lipid e.g. polymer conjugated lipid, preferably wherein the lipid-based carriers encapsulate the at least one nucleic acid, preferably the at least one RNA.In some specific embodiments, the lipid-based carrier, preferably the LNP, comprises(i) at least one cationic lipid selected from ALC-0315;(ii) at least one neutral lipid selected from DSPC;(iii) at least one steroid or steroid analog selected from cholesterol; and(iv) at least one aggregation reducing lipid selected from ALC-0159, preferably wherein i) to (iv) are in a molar ratio of about 47.4% cationic lipid, about 10% neutral lipid, about 40.9% steroid or steroid analogue, and about 1 .7% aggregation reducing lipid, preferably wherein the lipid-based carriers encapsulate the artificial nucleic acid or set.In preferred embodiments, the lipid-based carrier as defined herein, preferably the LNP as defined herein, encapsulates an artificial nucleic acid, preferably an mRNA, that comprises or consists of a nucleic acid sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 297-328, 694 or 695, or a fragment or variant of any of these sequences, preferably, wherein the RNA is preferably an mRNA that preferably has a 5’-cap structure.In particularly preferred embodiments, the lipid-based carrier as defined herein, preferably the LNP as defined herein, encapsulates an artificial nucleic acid, preferably an mRNA, that comprises or consists of a nucleic acid sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 328, or a fragment or variant of this sequence, preferably, wherein the RNA is an mRNA that preferably has a 5’-cap structure.In even more preferred embodiments, the lipid-based carrier as defined herein, preferably the LNP as defined herein, encapsulates an mRNA, that consists of a nucleic acid sequence which is identical to SEQ ID NO: 328, wherein the mRNA preferably has a 5’-cap structure.Alternatively, in particularly preferred embodiments, the lipid-based carrier as defined herein, preferably the LNP as defined herein, encapsulates an artificial nucleic acid, preferably an mRNA, that comprises or consists of a nucleic acid sequence which is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 694 or 695, or a fragment or variant of any of these sequences, preferably, wherein the RNA is an mRNA that preferably has a 5’-cap structure.In preferred embodiments, the wt / wt ratio of lipid to nucleic acid (e.g. RNA) in the lipid-based carrier, preferably the LNP, is from about 10:1 to about 60:1 , e.g. about 40:1. In embodiments, the wt / wt ratio of lipid to nucleic acid (e.g. RNA) is from about 20:1 to about 30:1 , e.g. about 25:1. In other preferred embodiments, the wt / wt ratio of lipid to nucleic acid (e.g. RNA) is in the range of 20 to 60, preferably from 3 to 15, 5 to 13, 4 to 8 or from 7 to 11 .The amount of lipid comprised in the lipid-based carrier such as the LNP may be selected taking the amount of the nucleic acid cargo into account. In one embodiment, these amounts are selected such as to result in an N / P ratio of the lipid-based carriers comprising the nucleic acid (e.g. RNA) in the range of about 0.1 to about 20. The N / P ratio is defined as the mole ratio of the nitrogen atoms (“N”) of the basic nitrogencontaining groups of the lipid to the phosphate groups (“P”) of the nucleic acid which is used as cargo. The N / P ratio may be calculated on the basis that, for example, 1 pg RNA typically contains about 3nmol phosphate residues, provided that the RNA exhibits a statistical distribution of bases. The “N”-value of the lipid or lipidoid may be calculated on the basis of its molecular weight and the relative content of permanently cationic and - if present - cationisable groups.In embodiments, the N / P ratio can be in the range of about 1 to about 50. In other embodiments, the range is about 1 to about 20, e.g. about 6 or about 14 or about 17. Preferably, the N / P ratio of the lipid-based carriers comprising the at least one nucleic acid (e.g. the RNA) is in a range from about 1 to about 20, preferably in a range from about 5 to about 7.In various embodiments, the composition comprises lipid-based carriers as defined herein such as LNPs as defined herein that have a defined size (particle size, homogeneous size distribution).The size of the lipid-based carriers such as LNPs is typically described herein as Z-average size. The terms “average diameter”, “mean diameter”, “diameter” or “size” for particles (e.g. lipid-based carrier) are used synonymously with the value of the Z-average. The term “Z-average size” refers to the mean diameter of particles as measured by dynamic light scattering (DLS) with data analysis using the so-called cumulant algorithm, which provides as results the so-called Z-average with the dimension of a length, and the polydispersity index (PI), which is dimensionless. The term “dynamic light scattering” or “DLS” refers to a method for analyzing particles in a liquid, wherein the liquid is typically illuminated with a monochromatic light source and wherein the light scattered by particles in the liquid is detected. DLS can thus be used to measure particle sizes in a liquid. Suitable DLS protocols are known in the art. DLS instruments are commercially available (such as the Zetasizer Nano Series, Malvern Instruments, Worcestershire, UK). DLS instruments employ either a detector at 90° (e.g., DynaPro® NanoStar® from Wyatt Technology or Zetasizer Nano S90® from Malvern Instruments) or a backscatter detection system at 173° (e.g., Zetasizer Nano S® from Malvern Instruments) and at 158° (DynaPro Plate Reader® from Malvern Instruments) close to the incident light of 180°. Typically, DLS measurements are performed at a temperature of about 25°C. DLS is also used in the context of the present invention to determine the polydispersity index (PDI) and / or the main peak diameter of the lipid-based carriers (e.g. LNPs) incorporating nucleic acid such as RNA.In preferred embodiments, the lipid-based carrier, preferably the LNP, has a Z-average size ranging from about 50nm to about 200nm, preferably in a range from about 50nm to about 150nm, more preferably from about 50nm to about 120nm.In preferred embodiments, at least 70% of the nucleic acid (e.g. RNA) comprised in the composition is encapsulated in lipid-based carriers such as LNPs, preferably 80% of the nucleic acid (e.g. RNA) comprised in the composition is encapsulated in lipid-based carriers such as LNPs, more preferably 90% of the nucleic acid (e.g. RNA) comprised in the composition is encapsulated in lipid-based carriers such as LNPs, most preferably 95% of the nucleic acid (e.g. RNA) comprised in the composition is encapsulated in lipid-based carriers such as LNPs, The percentage of encapsulation may be determined by a RiboGreen assay as known in the art.In embodiments, the plurality of the lipid-based carriers have a lamellar morphology and / or a bilayer morphology. In other embodiments, more than 90%, more than 95%, more than 96%, more than 97%, preferably, more than 98%, or more than 99% of the lipid-based carriers in a plurality of lipid-based carriers have a lamellar morphology and / or bilayer morphology. In preferred embodiments, at least about 80%, 85%, 90%, 95% of the lipid-based carriers such as LNPs have a spherical morphology, preferably comprising a solid core or a partially solid core, and / or a lamellar or bilayer morphology. In preferred embodiments, the surface of the lipid-based carrier, preferably the LNP, is uncharged at pH 7.In preferred embodiments, the composition comprises purified lipid-based carriers, preferably purified LNPs, comprising the nucleic acid as defined herein.In preferred embodiments, the composition is a liquid composition or a dried composition.In preferred embodiments, the composition is a lyophilized, a spray-dried or a spray-freeze dried composition. The composition may be lyophilized (e.g. according to WO2016165831 or WO2011069586) to yield a temperature stable and dried composition. The composition may also be dried using spray-drying or spray-freeze drying (e.g. according to WO2016184575 or WO2016184576) to yield a temperature stable dried composition.Lyoprotectants for lyophilization and / or spray drying or freezing may be selected from trehalose, sucrose, mannose, dextran and inulin. A preferred lyoprotectant is sucrose, optionally comprising a further lyoprotectant (e.g. trehalose). Accordingly, the composition may comprise at least one lyoprotectant as defined herein.In preferred embodiments, the composition comprises lipid-based carriers as defined herein encapsulating the artificial nucleic acid, preferably RNA, and are contained in a buffer system that comprises 50mM to 200mM glycerol, 50mM to 200mM sucrose, and Tris as a buffer agent. Such a buffer system is advantageous for storing the composition.In preferred embodiments, the composition is a liquid composition or a lyophilized / spray-dried composition reconstituted in a liquid carrier. In preferred embodiments, the composition is a liquid composition.In preferred embodiments, upon administration of the composition orthe artificial nucleic acid or the artificial nucleic acid set to a cell, tissue, or subject, the encoded at least one polypeptide or protein or at least two polypeptides or proteins are expressed.In preferred embodiments, upon administration of the composition orthe artificial nucleic acid orthe artificial nucleic acid set to a cell, tissue, or subject, the encoded combination of tumour antigens is produced, preferably in an amount sufficient for inducing an antigen specific immune response in said cell, tissue, or subject.In preferred embodiments, upon administration of the composition orthe artificial nucleic acid orthe artificial nucleic acid set to a cell, tissue, or subject, the encoded combination of tumour antigens is produced and induce an increased immunogenicity in the subject.In preferred embodiments, upon administration of the composition orthe artificial nucleic acid orthe artificial nucleic acid set to a cell, tissue, or subject, the encoded combination of tumour antigens is produced and induce an epitope-specific or antigen-specific CD8+ T cell response in the subject.In preferred embodiments, upon administration of the composition orthe artificial nucleic acid orthe artificial nucleic acid set to a cell, tissue, or subject, the encoded combination of tumour antigens is produced and induce an epitope-specific or antigen-specific CD4+ T cell response in the subject.In preferred embodiments, upon administration of the composition orthe artificial nucleic acid orthe artificial nucleic acid set to a cell, tissue, or subject, the encoded combination of tumour antigens is produced and induce humoral immunity, e.g. antibody titers and / or increased variety of antibody species against the encoded tumour antigens in the subject.In preferred embodiments, upon administration of the composition orthe artificial nucleic acid orthe artificial nucleic acid set to a cell, tissue, or subject, the encoded combination of tumour antigens is produced and increase IFN-gamma production by CD8+ T cells upon exposure to the encoded tumour antigens in the subject.In preferred embodiments, administration of the composition or the artificial nucleic acid or the artificial nucleic acid set to a cell, tissue, or subject, the encoded combination of tumour antigens is produced and increase the presentation of the encoded tumour antigens on MHC molecules in the subject.The term “presentation” of the encoded polypeptide or peptide (e.g. tumour antigens) relates to higher amount and / or variety of immunogenic and / or stable peptides presented via MHC class I and II moleculesafter protein degradation by the proteasomal machinery, and thus cellular immunity, e.g. T cell activation based thereon. The presentation of the encoded polypeptide or peptide on MHC class I and II molecules is increased on cells, comprising immune cells (e.g., T cells), antigen-presenting cells (e.g., dendritic cells, macrophages, engineered antigen-presenting cells), MHC class l-expressing cells, MHC class II- expressing cells, or any combination thereof.For example, the administration of the composition results in increased immunogenicity and / or presentation on MHC molecules of the encoded combination of tumour antigens that is increased by between about 0.1 % and about 100% (e.g., about 0.5%, 1 %, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, 95%, 98%, 99%, or about 100%) when compared to a subject that has not received the composition.In some embodiments, the administration of the composition results in immunogenicity and / or presentation on MHC molecules of the encoded combination of tumour antigens that is increased by about 2-fold to about 100-fold (e.g., about 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 12-fold, 14-fold, 16- fold, 18-fold, 20-fold, 25-fold, 30-fold, 40-fold, 50-fold, 60-fold, 70-fold, 80-fold, 90-fold, or about 100-fold) when compared to a subject that has not received the composition.In preferred embodiments, the pharmaceutical composition or the artificial nucleic acid or the artificial nucleic acid set is suitable for inducing a CD8 and / or CD4 immune response in a subject as defined herein against at least one of the encoded antigenic peptides or proteins from at least one of the TAAs BCAN, NLGNX4, PTPRZ1 , BIRC5 or ELOVL2, or from a variant thereof.In preferred embodiments, the pharmaceutical composition or the artificial nucleic acid or the artificial nucleic acid set is suitable for inducing a CD8 and / or CD4 immune response in a subject against- at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 MHC-I epitopes from the TAAs, more preferably against at least 1 , 2, 3, 4, 5, or 6 amino acid sequences or immunogenic fragments or variants as specified according to- SEQ ID NO: 130 (BCA-002) or an immunogenic fragment or variant thereof,- SEQ ID NO: 132 (NLGN4X-001) or an immunogenic fragment or variant thereof,- SEQ ID NO: 133 (PTP-003) or an immunogenic fragment or variant thereof,- SEQ ID NO: 134 (PTP-005) or an immunogenic fragment or variant thereof, and / or- SEQ ID NO: 136 (PTP-013) or an immunogenic fragment or variant thereof; and, optionally- SEQ ID NO: 138 (ELGVL2-001) or an immunogenic fragment or variant thereof; and / or- at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 MHC-II epitopes, more preferably against at least 1 , 2, or 3 amino acid sequences or immunogenic fragments or variants according to- SEQ ID NO: 137 (BIR-002) or an immunogenic fragment or variant thereof,- SEQ ID NO: 135 (PTP-010) or an immunogenic fragment or variant thereof, and / or- SEQ ID NO: 131 (BCA-005) or an immunogenic fragment or variant thereof.In preferred embodiments, the administration is an intramuscular, intratumoral, or intravenous administration, preferably an intramuscular, intratumoral, or intravenous injection.In particularly preferred embodiments of the invention, the pharmaceutical composition as defined herein is an immunogenic pharmaceutical composition, in particular an immunogenic pharmaceutical composition for inducing an immune response against TAAs as defined herein. Accordingly, the immunogenic pharmaceutical composition as defined herein is a cancer vaccine, in particular a glioblastoma and / or astrocytoma vaccine.4: Combination:In a fourth aspect, the invention provides a combination of at least two components of the foregoing aspects.It has to be noted that specific features and embodiments that are described in the context of the fourth aspect, that is the combination of the invention, are likewise applicable to any other aspect of the invention.In embodiments, the combination comprises the following components at least one or two artificial nucleic acid as defined in the context of the first aspect; and / or at least one or two artificial nucleic acid sets as defined in the context of the second aspect; and / or at least one or two pharmaceutical compositions as defined in the context of the third aspect.In preferred embodiments, the combination comprises at least two pharmaceutical compositions as defined herein.In preferred embodiments of the combination, the at least two pharmaceutical compositions together comprise at least two distinct artificial nucleic acids, wherein each of the at least two distinct artificial nucleic acids comprises at least one coding sequence encoding at least one polypeptide or protein, wherein the at least two encoded polypeptides or proteins together comprise at least one antigenic peptide or protein from each of the TAAs- BCAN or a variant thereof,- NLGNX4 or a variant thereof,- PTPRZ1 or a variant thereof, and- BIRC5 or a variant thereof.In preferred embodiments of the combination, the at least two pharmaceutical compositions comprises at least one distinct artificial nucleic acid as defined with respect to the at least two distinct artificial nucleic acids of a nucleic acid set as defined in the second aspect of the invention.In preferred embodiments of the combination, at least one, preferably each, of the pharmaceutical compositions is characterized by any of the features defined with respect to the third aspect of the invention.In embodiments, the combination additionally comprises at least one further component that is selected from a checkpoint inhibitor (in particular PD-1 , PDL-1 , CTLA4), a small molecule inhibitors, therapeutic antibodies or adoptive T-cells (in particular adoptive T-cells targeted against at least one TAA as specified herein).In preferred embodiments of the combination, the at least two pharmaceutical compositions and the at least one further component are administered in a spatially separated and / or timely staggered manner.5: Kit or kit of parts:In a fifth aspect, the invention provides a kit or kit of parts comprising at least one artificial nucleic acid, at least one artificial nucleic acid set, at least one composition, and / or at least one combination as defined in any of the foregoing aspects.It has to be noted that specific features and embodiments that are described in the context of the fifth aspect, that is the kit or kit of parts of the invention, are likewise applicable to any other aspect of the invention.In embodiments, the kit or kit of parts comprises at least one artificial nucleic acid of the first aspect, and / or at least one artificial nucleic acid set of the second aspect, and / or at least one composition of the third aspect, and / or at least one combination of the fourth aspect.In embodiments, the kit or kit of parts comprises a liquid vehicle for solubilising.In embodiments, the kit or kit of parts comprises technical instructions providing information on administration and dosage of the components. The technical instructions of said kit may contain information about administration and dosage and patient groups. Such kits, preferably kits of parts, may be applied e.g. for any of the applications or uses mentioned herein, preferably for the use of the therapeutic agents for the treatment of cancer or a diseases, disorder, or condition related to cancer.In embodiments where the nucleic acid or the pharmaceutical composition is provided as a lyophilized or spray-freeze dried or spray dried composition, the kit or kit of parts may additionally comprise a buffer for re-constitution of a lyophilized or a spray-freeze dried or a spray dried nucleic acid or composition.In preferred embodiments, the kit or kit of parts as defined herein comprises at least one syringe or application device. Suitably, in embodiments where lipid-based carrier formulated RNA is to be administered, a syringe or application device as described in WO2022207862, claims 1 to 69, may be part of the kit.6: Medical uses:In a sixth aspect, the present invention relates to the medical use of the therapeutic agents of the foregoing aspects.It has to be noted that specific features and embodiments that are described in the context of the sixth aspect, that is the medical use of the invention, are likewise applicable to any other aspect of the invention. In particular, specific features and embodiments relating to medical uses as provided herein may also apply to method of treatments of the invention and vice versa.Accordingly, the invention provides an artificial nucleic acid as defined in the context of the first aspect, an artificial nucleic acid set as defined in the context of the second aspect, a pharmaceutical composition as defined in the context of the third aspect, at least two pharmaceutical compositions of the combination as defined in the context of the fourth aspect, or a kit or kit of parts as defined in the context of the fifth aspect for use as a medicament.In preferred embodiments, the use may be for human medical purposes and also for veterinary medical purposes, preferably for human medical purposes.In preferred embodiments, the use may be for human medical purposes for subjects that have cancer.Accordingly, the invention provides an artificial nucleic acid as defined in the context of the first aspect, an artificial nucleic acid set as defined in the context of the second aspect, a pharmaceutical composition as defined in the context of the third aspect, at least two pharmaceutical compositions of the combination as defined in the context of the fourth aspect, or a kit or kit of parts as defined in the context of the fifth aspect for use as a medicament in treating or preventing cancer in a subject, or any disease, disorder, or condition related to cancer.As used herein, the term “cancer” refers to a neoplasm characterized by the uncontrolled and usually rapid proliferation of cells that tend to invade surrounding tissue and to metastasize to distant body sites. The term encompasses benign and malignant neoplasms. Malignancy in cancers is typically characterized by anaplasia, invasiveness, and metastasis; whereas benign malignancies typically have none of those properties. The terms includes neoplasms characterized by tumour growth as well as cancers of blood and lymphatic system. The term “cancer” according to the disclosure also comprises cancer metastases, e.g. cancer metastases associated with glioblastoma or astrocytoma.In some embodiments, the treating or preventing cancer in a subject is a personalized treatment. Accordingly, prior to a treatment with the respective therapeutic agents, the cancer of the patient may be analyzed by e.g. sequencing and / or mass spectrometry based tumour HLA-ligandome analysis.In embodiments, the cancer is selected from any tumour of the CNS as shown in Table 2.Table 2: Suitable Tumours of the Central Nervous System. Provisional Entities are in ItalicsAbbreviations: CNS, central nervous system; IDH, isocitrate dehydrogenase; NK, natural killer; PitNET, pituitary neuroendocrine tumor; SHH, sonic hedgehog.In preferred embodiments, the cancer is selected from a brain tumour, in particular selected from gliomas.Gliomas are brain tumours originating from glial cells in the nervous system. Glial cells, commonly called neuroglia or simply glia, are non-neuronal cells that provide support and nutrition, maintain homeostasis, form myelin, and participate in signal transmission in the nervous system. The two most important subgroups of gliomas are astrocytomas and oligodendrogliomas, named according to the normal glial cell type from which they originate (astrocytes or oligodendrocytes, respectively). Belonging to the subgroup of astrocytomas, glioblastoma multiforme (referred to as glioblastoma hereinafter) is the most common malignant brain tumour in adults and accounts for approx. 40% of all malignant brain tumours and approx. 50% of gliomas. It aggressively invades the central nervous system and is ranked at the highest malignancy level (grade IV) among all gliomas. Although there has been steady progress in their treatment due to improvements in neuroimaging, microsurgery, diverse treatment options, such as temozolomide or radiation, glioblastomas remain incurable. The lethal rate of this brain tumour is very high: the average life expectancy is 9 to 12 months after first diagnosis. The 5-year survival rate during the observation period from 1986 to 1990 was 8.0%. To date, the five-year survival rate following aggressive therapy including gross tumour resection is still less than 10%.Tumour cells of glioblastomas (GBM) are the most undifferentiated ones among brain tumours, so the tumour cells have high potential of migration and proliferation and are highly invasive, leading to very poor prognosis. Glioblastomas lead to death due to rapid, aggressive, and infiltrative growth in the brain. The infiltrative growth pattern is responsible for the unresectable nature of these tumours. Glioblastomas are also relatively resistant to radiation and chemotherapy, and, therefore, post-treatment recurrence rates are high. In addition, the immune response to the neoplastic cells is rather ineffective in completely eradicating all neoplastic cells following resection and radiation therapy.The average annual incidence rate of GBM is variable, ranging from 0.59 per 100,000 persons to 3.69 per 100,000 persons, and is the highest among malignant primary brain tumours.GBM is classified into primary glioblastoma (de novo) and secondary glioblastoma, depending on differences in the gene mechanism during malignant transformation of undifferentiated astrocytes or glial precursor cells. GBM (CNS WHO Grade 4) mainly occurs in older patients (mean age of 64 years), and typically shows epidermal growth factor receptor over expression, PTN (MMC I) mutation, CDKN2A (p16) deletion, and less frequently MDM2 amplification. The presence of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation is a positive predictor of better overall survival (OS). Astrocytoma (CNS WHO Grade 2, 3 and 4) or oligodendrogliomas (CNS WHO Grade 2 and 3) mainly occur in younger patients (mean age of 45 years) and often contain TP53 mutations as the earliest detectable alteration. Mutations in isocitrate dehydrogenase-1 (IDH1) and IDH2 are present in 70 to 80% of astrocytomas (CNS WHO Grade 2, 3 and 4), and in only 5 to 10% of GBMs (CNS WHO Grade 4).Accordingly, in preferred embodiments, the cancer is glioblastoma or astrocytoma.In alternative embodiments, the cancer is selected from WHO grade II astrocytoma, WHO grade III astrocytoma, WHO grade II oligodendroglioma, WHO grade III oligodendroglioma or ependymoma.In alternative embodiments, the cancer is selected from any other brain, neuronal or tumour of the central nervous system, wherein at least one ofthe particularly preferred TAAs BCAN, PTPRZ1 , NLGN4X or BIRC- 5 is expressed or overexpressed.Accordingly, the invention provides an artificial nucleic acid as defined in the context of the first aspect, an artificial nucleic acid set as defined in the context of the second aspect, a pharmaceutical composition as defined in the context of the third aspect, at least two pharmaceutical compositions of the combination as defined in the context of the fourth aspect, or a kit or kit of parts as defined in the context of the fifth aspect for use as a medicament in treating or preventing glioblastoma or astrocytoma in a subject, or any disease, disorder, or condition related to glioblastoma or astrocytoma.In preferred embodiments in that context, the glioblastoma or astrocytoma is i) MGMT-unmethylated glioblastoma or ii) astrocytoma with a molecular signature of unmethylated glioblastoma.Accordingly, the invention provides an artificial nucleic acid as defined in the context of the first aspect, an artificial nucleic acid set as defined in the context of the second aspect, a pharmaceutical composition as defined in the context of the third aspect, at least two pharmaceutical compositions of the combination as defined in the context of the fourth aspect, or a kit or kit of parts as defined in the context of the fifth aspect for use as a medicament in treating or preventing i) MGMT-unmethylated glioblastoma or ii) astrocytoma with a molecular signature of unmethylated glioblastoma in a subject.In preferred embodiments in that context, the glioblastoma or astrocytoma is i) “unmethylated” glioblastoma of CNS WHO Grade 4 (according to the 5th edition of the WHO Classification of Tumors of the CentralNervous System, Volume 6) or ii) isocitrate dehydrogenase (IDH)-wild type astrocytoma with a molecular signature of “unmethylated” glioblastoma.Accordingly, the invention provides an artificial nucleic acid as defined in the context of the first aspect, an artificial nucleic acid set as defined in the context of the second aspect, a pharmaceutical composition as defined in the context of the third aspect, at least two pharmaceutical compositions of the combination as defined in the context of the fourth aspect, or a kit or kit of parts as defined in the context of the fifth aspect for use as a medicament in treating or preventing i) “unmethylated” glioblastoma of CNS WHO Grade 4 (according to the 5th edition of the WHO Classification of Tumors of the Central Nervous System, Volume 6) or ii) isocitrate dehydrogenase (IDH)-wild type astrocytoma with a molecular signature of “unmethylated” glioblastoma in a subject.In preferred embodiments of the medical uses provided herein, the artificial nucleic acid, the artificial nucleic acid set, the pharmaceutical composition, the at least two pharmaceutical compositions of the combination, or the kit or kit of parts are administered to the subject by intramuscular, intradermal, intratumoral, or intravenous administration.In particularly preferred embodiments, the administration is an intramuscular administration.In particularly preferred embodiments of the medical uses provided herein, the artificial nucleic acid is an mRNA comprising or consisting of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the nucleic acid sequence SEQ ID NO: 328, or a fragment or variant of these, preferably, wherein the mRNA preferably has a 5’-cap structure, preferably, wherein said artificial nucleic acid is administered in form of a pharmaceutical composition, preferably formulated in lipid-based carriers as defined herein (in particular LNPs as defined herein).In even more preferred embodiments of the medical uses provided herein, the mRNA is identical to SEQ ID NO: 328, wherein the mRNA preferably has a 5’-cap structure, preferably, wherein said artificial nucleic acid is administered in form of a pharmaceutical composition, preferably formulated in lipid-based carriers as defined herein (in particular LNPs as defined herein).Alternatively, in particularly preferred embodiments of the medical uses provided herein, the artificial nucleic acid is an mRNA comprising or consisting of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the nucleic acid sequence SEQ ID NOs: 694 or 695, or a fragment or variant of these, preferably, wherein the mRNA preferably has a 5’-cap structure, preferably, wherein said artificial nucleic acid is administered in form of a pharmaceutical composition, preferably formulated in lipid-based carriers as defined herein (in particular LNPs as defined herein).In particularly preferred embodiments of the medical uses provided herein, the subject is a human, preferably an adult human subject.In preferred embodiments in that context, the subject is newly-diagnosed.In preferred embodiments in that context, the subject has previously undergone surgery, radiotherapy and / or chemotherapy, preferably surgery and radiotherapy and, optionally, a chemotherapy.In specific embodiments, the subject that has previously undergone surgery, has received postsurgical radiation therapy (RT), either alone or in combination with concurrent temozolomide (TMZ) chemotherapy, optionally followed by TMZ maintenance.In preferred embodiments in that context, the subject expresses at least one HLA-A*02 allele, preferably expresses HLA-A*02:01 .In preferred embodiments in that context, the subject’s HLA subtype and / or antigen expression and / or tumour epitope presentation is assessed prior to treatment or prevention, e.g. by sequencing and / or mass spectrometry based tumour HLA-ligandome analysis.In particularly preferred embodiments of the medical uses provided herein, the artificial nucleic acid, the artificial nucleic acid set, the at least one pharmaceutical composition, the at least two pharmaceutical compositions of the combination, or the kit or kit of parts comprises a coding sequence encoding at least one antigenic peptide or protein from at least one of the TAAs BCAN, NLGNX4, PTPRZ1 , BIRC5 or ELOVL2, or from a variant thereof, comprising or consisting of at least one MHC-I epitope, wherein the at least one MHC-I epitope is an HLA-A / B / C epitope other than a HLA-A*02 or a HLA-A*02:01 epitope.In particularly preferred embodiments of the medical uses provided herein, the artificial nucleic acid, the artificial nucleic acid set, the at least one pharmaceutical composition, the at least two pharmaceutical compositions of the combination, or the kit or kit of parts comprises a coding sequence encoding at least one antigenic peptide or protein from at least one of the TAAs BCAN, NLGNX4, PTPRZ1 , BIRC5 or ELOVL2, or from a variant thereof, comprising or consisting of at least one MHC-I epitope, wherein the at least one MHC-I epitope is an HLA-A / B / C epitope, wherein HLA-A / B / C is an allele expressed by at least 5, 10, 15, 20, 25, 30, 35, 40, 50, or 60% of the human population in Europe, North America and / or Asia.In preferred embodiments, the artificial nucleic acid, the artificial nucleic acid set, the at least one pharmaceutical composition, the at least two pharmaceutical compositions of the combination, or the kit or kit of parts is suitable for vaccination of subjects that do not express HLA-A allele HLA-A*02 or HLA- A*02:01.In preferred embodiments, the artificial nucleic acid, the artificial nucleic acid set, the at least one pharmaceutical composition, the at least two pharmaceutical compositions of the combination, or the kit orkit of parts comprises a coding sequence encoding at least one at least one MHC-I and / or MHC-II epitope that is present and / or predicted to be present in at least 20, 30, 40, 50, 60, 70, 80, 90, 95, 96, 97, 98, 99% or in 100% of, optionally newly-diagnosed and / or surgically resected, subjects with- glioblastoma and / or astrocytoma,- MGMT-unmethylated glioblastoma and / or astrocytoma with a molecular signature of unmethylated glioblastoma, and / or- “unmethylated” glioblastoma of CNS WHO Grade 4 (according to the 5th edition of the WHO Classification of Tumors of the Central Nervous System, Volume 6) and / or isocitrate dehydrogenase (IDH)-wild type astrocytoma with a molecular signature of “unmethylated” glioblastoma.In preferred embodiments in that context, the artificial nucleic acid, the artificial nucleic acid set, the at least one pharmaceutical composition, the at least two pharmaceutical compositions of the combination, or the kit or kit of parts is suitable for vaccination of at least 20, 30, 40, 50, 60, 70, 80, 90, 95, 96, 97, 98, 99% or 100% of said subjects.In preferred embodiments of the medical uses provided herein, the subject’s HLA subtype and / or antigen expression and / or tumour epitope presentation does not have to be assessed prior to treatment.In preferred embodiments of the medical uses provided herein, the treatment or prevention regime comprises a main period, preferably approximately 10 weeks of vaccination, and an optional maintenance period, preferably approximately 36 weeks of vaccination.In preferred embodiments of the medical uses provided herein, treatment or prevention regime comprises vaccinations at approximately days 1 , 8, 15, 29, 43, 57, and / or 71 in the main period, and optionally comprises vaccinations at approximately days 113, 155, 197, 239, 281 and / or 323 in the maintenance period.Approximately in this specific context preferably means +5 / -5, +4 / -4, +3 / -3, +21-2, +1 / -1 days compared to the indicated days.In preferred embodiments of the medical uses provided herein, the treatment or prevention regime comprises a vaccination dose per day of 12-1000pg mRNA, more preferably 12-100pg, most preferably approximately 12, 25, 50 or 100pg mRNA.In preferred embodiments of the medical uses provided herein, the treatment or prevention regime comprises a combination with at least one modality selected from radiotherapy, chemotherapy, checkpoint inhibitors, small molecule inhibitors, therapeutic antibodies or adoptive T-cell therapy.A preferred chemotherapeutic agent in that context is temozolomide.Preferred checkpoint inhibitors in that context are e.g.:CTLA4 inhibitors (such as anti-CTLA4 antibodies Ipilimumab and Tremelimumab)PD1 inhibitors (such as anti-PD1 antibodies Nivolumab, Pembrolizumab and Cemiplimab or anti- PDL1 antibodies Atezolizumab, Avelumab und Durvalumab).LAG3 antibodiesThis is not a conclusive list and the skilled person in the art will readily find more alternatives.In preferred embodiments in that context, the combination of the vaccination and the at least one modality is concurrently and / or sequentially.In preferred embodiments in that context, the vaccination is combined with temozolomide and / or a PD1 checkpoint inhibitor.In preferred embodiments of the medical uses provided herein, the artificial nucleic acid, the artificial nucleic acid set, the at least one pharmaceutical composition, the at least two pharmaceutical compositions of the combination, or the kit or kit of parts is administered as monotherapy.In preferred embodiments of the medical uses provided herein, the artificial nucleic acid, the artificial nucleic acid set, the at least one pharmaceutical composition, the at least two pharmaceutical compositions of the combination, or the kit or kit of parts induces a CD8 and / or CD4 immune response in a subject as defined in claim 148 against at least one of the encoded antigenic peptides or proteins from at least one of the TAAs BCAN, NLGNX4, PTPRZ1 , BIRC5 or ELOVL2, or from a variant thereof.In preferred embodiments of the medical uses provided herein, the artificial nucleic acid, the artificial nucleic acid set, the at least one pharmaceutical composition, the at least two pharmaceutical compositions of the combination, or the kit or kit of parts induces a CD8 and / or CD4 immune response in a subject as defined herein against- at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 MHC-I epitopes from the TAAs, more preferably against at least 1 , 2, 3, 4, 5, or 6 amino acid sequences or immunogenic fragments or variants as specified herein in the context of the first aspect, and / or- at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 MHC-II epitopes, more preferably against at least 1 , 2, or 3 amino acid sequences or immunogenic fragments or variants as specified herein in the context of the first aspect.In particularly preferred embodiments of the medical uses provided herein, the treatment inhibits tumour growth and / or results in tumour shrinkage and / or results in the elimination of the tumour treatment.7: Methods of treatment:In a seventh aspect, the present invention relates to a method of treating or preventing a disease, disorder or condition.It has to be noted that specific features and embodiments that are described in the context of the seventh aspect, that is the methods of treatment of the invention, are likewise applicable to any other aspect of theinvention. In particular, specific features and embodiments relating to method of treatments as provided herein may also apply for medical uses of the invention and vice versa.Preventing (inhibiting) or treating a disease relates to inhibiting the full development of a disease or condition, for example, in a subject who is at risk for a disease such as an infection or cancer. “Treatment” refers to a therapeutic intervention that ameliorates a sign or symptom of a disease or pathological condition after it has begun to develop. The term “ameliorating”, with reference to a disease or pathological condition, refers to any observable beneficial effect of the treatment. Inhibiting a disease can include preventing or reducing the risk of the disease. The beneficial effect can be evidenced, for example, by a delayed onset of clinical symptoms of the disease in a susceptible subject, a reduction in severity of some or all clinical symptoms of the disease, a slower progression of the disease, an improvement in the overall health or wellbeing of the subject, or by other parameters that are specific to the particular disease. A “prophylactic” treatment is a treatment administered to a subject who does not exhibit signs of a disease or exhibits only early signs for the purpose of decreasing the risk of developing pathology.Accordingly, the invention provides a method of treating or preventing a disease, disorder or condition, wherein the method comprises applying or administering to a subject in need thereof an effective amount of an artificial nucleic acid of the first aspect, an artificial nucleic acid set of the second aspect, at least one pharmaceutical composition of the third aspect, at least two pharmaceutical compositions of the combination of fourth aspect, or a kit or kit of parts of the fifth aspect.As used herein, “effective” when referring to an amount of a therapeutic compound refers to the quantity of the compound that is sufficient to yield a desired therapeutic response without undue adverse side effects (such as toxicity, irritation, or allergic response) commensurate with a reasonable benefit / risk ratio when used in the manner of this disclosure.In preferred embodiments, the method of treating or preventing a disease, disorder or condition is further characterized by any of the features and embodiments that are inter alia provided in the section “Medical use” of the sixth aspect.In particularly preferred embodiments, the disease, disorder or condition is a cancer disease, disorder or condition, preferably a cancer disease, disorder or condition of the CNS, preferably any cancer disease, disorder or condition of the CNS as provided in Table 2, even more preferably glioblastoma or astrocytoma.In particularly preferred embodiments, the artificial nucleic acid is an mRNA comprising or consisting of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the nucleic acid sequence SEQ ID NO: 328, or a fragment or variant of these, preferably, wherein the mRNA preferably has a 5’-cap structure, wherein said artificial nucleic acid is preferably administered in form of a pharmaceutical composition, wherein the mRNA is preferably formulated in lipid-based carriers as defined herein (in particular LNPs as defined herein).In even more preferred embodiments, the mRNA is identical to SEQ ID NO: 328, wherein the mRNA preferably has a 5’-cap structure, wherein said artificial nucleic acid is preferably administered in form of a pharmaceutical composition, wherein the mRNA is preferably formulated in lipid-based carriers as defined herein (in particular LNPs as defined herein).Alternatively, in particularly preferred embodiments, the artificial nucleic acid is an mRNA comprising or consisting of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to the nucleic acid sequence SEQ ID NOs: 694 or 695, or a fragment or variant of these, preferably, wherein the mRNA preferably has a 5’-cap structure, wherein said artificial nucleic acid is preferably administered in form of a pharmaceutical composition, wherein the mRNA is preferably formulated in lipid-based carriers as defined herein (in particular LNPs as defined herein).8: Modulator element:In further aspects, the invention provides a modulator element that is inter alia suitable for improving the processing and / or presentation of e.g. a tumour antigen.8.1. Artificial nucleic acid encoding a modulator elementIn certain aspects, the invention provides an artificial nucleic acid comprising at least one coding sequence, wherein the at least one coding sequence encodes at least one encoded polypeptide or protein, the at least one polypeptide or protein comprising at least one antigenic peptide or protein and at least one amino acid sequence from a modulator element, wherein the modulator element modulates / impacts the expression / translation of production of and / or stability of and / or degradation of and / or intracellular protein amount of and / or turnover of and / or processing for presentation by MHC molecules of and / or retention time in endosomal-lysosomal vesicles of and / or epitope presentation on MHC molecules of the at least one encoded polypeptide or protein, preferably wherein the modulator element is a heterologous element.In particularly preferred embodiments, the modulator element modulates / impacts turnover of and / or processing for presentation by MHC molecules of and / or epitope presentation on MHC molecules of the at least one encoded polypeptide or protein.“Heterologous” and “modulation” preferably have the meaning as defined in the first aspect.In particularly preferred embodiments, the modulator element is a degron.In preferred embodiments, the modulator element is a ubiquitin-dependent degron.In preferred embodiments, the modulator element, preferably a degron, comprises at least one recognition site for an E3 ubiquitin ligase preferably for a Cullin-RING E3 type ubiquitin ligase, most preferably for a Cul4DCAF12 Cullin-RING type E3 ubiquitin ligase.In preferred embodiments, the modulator element, preferably a degron, is located at the N-terminus of, at the C-terminus of, or within the amino acid sequence of the at least one encoded polypeptide or protein.In preferred embodiments, the degron comprises or consists of an amino acid sequence- of at least 2, 3, 4, or 5, preferably of 5 glutamic acids and is preferably located at the C-terminus of the at least one encoded polypeptide or protein,- of at least 2, 3, 4, or 5, preferably of 5 glycines, and is preferably located at the C-terminus of the at least one encoded polypeptide or protein,- of at least 2, 3, 4, or 5, preferably of 5 arginines, and is preferably located at the N- or C-terminus of the at least one encoded polypeptide or protein, or- of at least 2, 3, 4, or 5, preferably of 5 lysines, and is preferably located at the N-terminus of the at least one encoded polypeptide or protein.In particularly preferred embodiments, the degron comprises or consists of an amino acid sequence of at least 2, 3, 4, or 5, preferably of 5 glutamic acids and located at the C-terminus of the at least one encoded polypeptide or protein.In preferred embodiments, the at least one encoded polypeptide or protein comprising the modulator element, preferably a degron, is characterized by- a decreased folding of, and / or- a decreased stability of, and / or- an increased degradation of, and / or- a decreased intracellular protein amount of, and / or- an increased turnover of, and / or- an increased processing for presentation by MHC-I and / or MHC-II molecules of, and / or- an increased retention time in endosomal-lysosomal vesicles of, and / or- an increased loading of MHC-I and / or MHC-II molecules, and / or- an increased epitope presentation on MHC-I and / or MHC-II molecules upon artificial nucleic acid administration compared to a corresponding polypeptide or protein without the modulator element.In preferred embodiments, the at least one encoded polypeptide or protein comprising the modulator element, preferably a degron, more preferably a degron as defined herein, more preferably a degron comprising or consisting of an amino acid sequence of at least 2, 3, 4, or 5 glutamic acids, additionally comprises at least one additional amino acid sequence selected from an IRSTepm or from a variant thereof.In preferred embodiments in that context, the at least one additional amino acid sequence selected from an IRSTepm or from a variant thereof is an amino acid sequence from CTLA4 or from a variant thereof, preferably the amino acid sequence according to SEQ ID NO: 201 (TM / CD-CTLA4), or a fragment or variant thereof, wherein the amino acid sequence is preferably encoded by a nucleic acid sequence according to SEQ ID NO: 296 or SEQ ID NO: 672, or a fragment or variant thereof.In preferred embodiments in that context, the at least one additional amino acid sequence is located C- terminally of the most C-terminal antigenic peptide or protein, or of a linker element fused C-terminally to said antigenic peptide or protein.In even more preferred embodiments, the modulator element is directly located C-terminally of an additional amino acid sequence from an IRSTepm as defined herein, i.e. not separated by any linker element and / or any other amino acid sequence.In preferred embodiments, the modulator element, preferably a degron, more preferably a degron as defined herein, most preferably a degron comprising or consisting of an amino acid sequence of at least 2, 3, 4, or 5 glutamic acids, is located C-terminally of an additional amino acid sequence selected from an IRSTepm, preferably located C-terminally of an additional amino acid sequence from an IRSTepm as defined herein.In preferred embodiments, the at least one encoded polypeptide or protein is selected from an antigen, preferably a tumour or cancer antigen.In preferred embodiments, the at least one encoded polypeptide or protein comprising the modulator element, preferably a degron, is characterized by- an increased expression / translation of, and / or- an increased production of, and / or- an increased folding of, and / or- an increased stability of, and / or- a decreased degradation of, and / or- an increased intracellular protein amount of, and / or- an decreased turnover of, and / or- an increased processing for presentation by MHC-I and / or MHC-II molecules of, and / or- an increased retention time in endosomal-lysosomal vesicles of, and / or- an increased loading of MHC-I and / or MHC-II molecules, and / or- an increased epitope presentation on MHC-I and / or MHC-II molecules upon artificial nucleic acid administration compared to a corresponding polypeptide or protein without the modulator element.In preferred embodiments, the at least one encoded polypeptide or protein comprising the modulator element, preferably a degron, is characterized by an increased intracellular protein amount upon artificial nucleic acid administration compared to a corresponding polypeptide or protein without the modulator element.In preferred embodiments, the at least one encoded polypeptide or protein comprising the modulator element, preferably a degron, is characterized by an increased presentation of at least one MHC-II epitopecomprised in the at least one encoded polypeptide or protein upon artificial nucleic acid administration compared to a corresponding polypeptide or protein without the modulator element.In preferred embodiments, the nucleic acid is characterized by any one of the general nucleic acid features and embodiments as described in the context of the first aspect, section “Nucleic acid sequence features and embodiments” .In particularly preferred embodiments of the present aspect, the nucleic acid is an RNA, preferably an mRNA.8.2. A composition comprising an artificial nucleic acid encoding a modulator elementIn certain aspects, the invention provides a composition of the artificial nucleic acid as defined in aspect 8.1 , wherein the composition is characterized by any one of the general composition features as defined with respect to the pharmaceutical composition in the context of the third aspect.8.3. A polypeptide or protein comprising or consisting of a modulator elementIn certain aspects, the invention provides a polypeptide or protein comprising or consisting of a modulator element, wherein the modulator element and the polypeptide or protein are characterized by any one of the features as defined in aspects 8.1 and 8.2. Suitably, the modulator element is a degron as defined herein.In preferred embodiments, the modulator element, preferably the degron, comprises or consists of an amino acid sequence- of at least 2, 3, 4, or 5, preferably of 5 glutamic acids and is preferably located at the C-terminus of the at least one encoded polypeptide or protein,- of at least 2, 3, 4, or 5, preferably of 5 glycines, and is preferably located at the C-terminus of the at least one encoded polypeptide or protein,- of at least 2, 3, 4, or 5, preferably of 5 arginines, and is preferably located at the N- or C-terminus of the at least one encoded polypeptide or protein, or- of at least 2, 3, 4, or 5, preferably of 5 lysines, and is preferably located at the N-terminus of the at least one encoded polypeptide or protein.In particularly preferred embodiments the modulator element, preferably the degron, comprises or consists of an amino acid sequence of at least 2, 3, 4, or 5, preferably of 5 glutamic acids and is located at the C- terminus of the at least one encoded polypeptide or protein.8.4. Use of a modulator elementIn certain aspects, the invention provides the use of an artificial nucleic acid encoding a modulator element, preferably a degron, or the use of a polypeptide or protein comprising or consisting of a modulator element for modulating the expression / translation of and / or stability of and / or degradation of and / or intracellular protein amount of and / or turnover of and / or processing for presentation by MHC molecules of and / orepitope presentation on MHC molecules of the at least one encoded polypeptide or protein, preferably wherein the modulator element is a heterologous element.In particularly preferred embodiments of the use, the modulator element modulates / impacts turnover of and / or processing for presentation by MHC molecules of and / or epitope presentation on MHC molecules of the at least one encoded polypeptide or protein.Suitably, the artificial nucleic acid encoding a modulator element may be further characterized by features as defined in aspect 8.1 and the polypeptide or protein comprising or consisting of a modulator element may be further characterized by features as defined in aspect 8.3.Further aspects relating to the modulator element of the invention:In further aspects, the invention provides a nucleic acid cassette encoding a modulator element, wherein the modulator element is characterized by any one of the features as defined herein, preferably wherein the nucleic acid cassette encodes for a degron as a modulator element, optionally wherein the nucleic acid cassette is characterized by any one of the general nucleic acid features as defined with respect to the artificial nucleic acid (see first aspect, “nucleic acid features and embodiments”).In further aspects, the invention provides a modulator element, wherein the modulator element is characterized by any one of the features as defined herein, preferably wherein the modulator element comprises an amino acid sequence as defined in herein, preferably comprising least 2, 3, 4, or 5, preferably of 5 glutamic acids and located at the C-terminus of the at least one encoded polypeptide or protein.In further aspects, the invention provides a kit or kit of parts comprising an artificial nucleic acid encoding a modulator element as defined herein, and / or at least one composition comprising an artificial nucleic acid encoding a modulator element as defined herein, and / or at least one nucleic acid cassette encoding a modulator element as defined herein, and / or at least one polypeptide or protein comprising a modulator element as defined herein, and / or at least one modulator element as defined herein, optionally comprising a liquid vehicle for solubilising, and optionally comprising technical instructions providing information on administration and dosage of the components.In further aspects, the invention provides an artificial nucleic acid encoding a modulator element as defined herein, and / or at least one composition comprising an artificial nucleic acid encoding a modulator element as defined herein, and / or at least one nucleic acid cassette encoding a modulator element as defined herein, and / or at least one polypeptide or protein comprising a modulator element as defined herein, and / or at least one modulator element as defined herein, and a kit or kit of parts as defined herein, for use as a medicament, preferably for use as a medicament in treating or preventing cancer or an infectious disease in a subject, or any disease, disorder, or condition related to cancer or infectious diseases.Brief Description of the FiguresFigure 1 shows the schematic representations of the CVGBM mRNA (R11047) and of the encoded fusion protein. The encoded protein consists of the SP of CTLA4 (aa 1 -35), 9 antigenic peptides of 29aa each (1 : PTPRZ1 (aa 27-55; comprises PTP-010), 2: PTPRZ1 (aa 185-213; comprises PTP-003), 3: PTPRZ1 (aa 1337-1365; comprises PTP-005), 4: PTPRZ1 (aa 1804-1832; comprises PTP-013), 5: NLGN4X (aa 121-149; comprises NLGN4X-001), 6: BCAN (aa 92-120; comprises BCA-005), 7: BCAN (aa 473-501 ; comprises BCA-002), 8: BIRC5 (aa 90-118; comprises BIR-002), 9: HBV capsid protein (aa 8-36; comprises HBV-001)), the TM / CD of CTLA4 (aa 162-223), and a C-terminal E5 degron, all but the last separated by linkers (G4S). aa= amino acid residues; CTLA4 = cytotoxic T-lymphocyte-associated protein 4; GBM = glioblastoma; HBVc = HBV capsid protein; MHC-I / II = major histocompatibility complex class l / ll; ORF = open reading frame; SP = signal peptide; TM / CD = transmembrane and cytosolic domain; UTR = untranslated region.Figure 2 shows the schematic representation of fusion proteins encoded by further mRNAs used in the Examples. R11052 and R11053 are surrogate mRNAs with and without C-terminal E5 degron, respectively, which additionally comprise a reporter module. The latter comprises three antigenic peptides of 29 aa each (H2-Ea (aa 71-99; comprises Ea), SERPINB14 (aa 247-275; comprises SIINFEKL) and PRAME (aa 290-318)) as well as a 3xHA tag (31 aa). Further details / abbreviations are found in the legend of Figure 1.Figure 3 shows the schematic representation of the fusion protein encoded by B16-CTLA4-E5 (R10667), which is used in Example 5. This mRNA encodes a fusion protein consisting of the SP of CTLA4 (aa 1 -35), 10 antigenic peptides derived from the B16.F10 melanoma cell line of 29 aa each (1 : Pmel (aa 14-42; S26P), 2: Det (aa 170-198), 3: Pbk (aa 131-159; V145D), 4: Trp1 (aa 445-473; A463M), 5: Obsll (aa 1750-1778; T1764M), 6: Plod2 (aa 516-544; F530V), 7: Intsl 1 (aa 300- 328; D314N), 8: Kif18b (aa 725-753; K739N), 9: Atp1 1 a (aa 508-536; R522S), 10: Trp53 (aa 220-248; M234I)), the PADRE epitope (13 aa), the TM / CD of CTLA4 (aa 162-223), and a C- terminal E5 degron, all but the last separated by G4S-linkers. Further details / abbreviations are found in the legend of Figure 1 .Figure 4 shows the expected patient coverage for a vaccine comprising the eight particularly preferred GBM antigenic peptides from 4 TAAs among glioblastoma. Each point represents the result of one simulation of a clinical trial with 50 patients, the simulations were repeated 100 times. The y-axis shows the expected coverage. The x-axis shows the minimum number of antigens that generate epitopes that cover patients. For example, if the “minimum number of antigens considered” (see Fig. 4, x-axis) is “1 ”, then the patients are covered by the vaccine if they bind any MHC-I epitope from at least one antigen. Since the coverage estimations were only based on the sequences of the particularly preferred antigenic peptide sequences and not on the full- length TAA sequences, “any epitope from at least one antigen” means the following: i) regarding BCAN this means at least one MHC-I epitope within BCA-002-long or BCA-005-long; ii)regarding PTPRZ1 , this means at least one MHC-I epitope within PTP-003-long, PTP-005-long, PTP-010-long or PTP-013-long; iii) regarding NLGN4X and BIRC-5, this means at least one MHC-I epitope within NLGN4X-001-long or BIR-002-long, respectively.Figure 5 shows the expected patient coverage for a vaccine comprising the eight particularly preferred GBM antigenic peptides from 4 TAAs among glioblastoma patients expressing at least the HLA- A*02:01 allele. Each point represents the result of one simulation of a clinical trial with 50 patients, the simulations were repeated 100 times. For more information, see legend of Figure 4 and Example 2.2.Figure 6 shows the frequency of HA-positive cells detected by intracellular flow cytometry of fresh bone marrow-derived dendritic cells (BMDCs) of C57BL / 6 mice 9h after electroporation with the indicated mRNA constructs. Bars indicate median values of two technical replicates.Figure 7 shows the frequency of HA-positive cells detected by intracellular flow cytometry of JAWSII cells (murine immature DC cell line) 24h after lipofection with the indicated mRNA constructs. Bars indicate median values of two technical replicates.Figure 8 shows the frequency of HA-positive cells detected by intracellular flow cytometry of HeLa cells 24h after lipofection with the indicated mRNA constructs. Bars indicate median values of two technical replicates.Figure 9 shows the presentation of the surrogate MHC-I epitope SIINFEKL (Figure 9A) and MHC-II epitope Ea (Figure 9B) as percentage of SIINFEKL pMHC+ and Ea pMHC+ cells, respectively, detected by flow cytometry on fresh BMDCs of C57BL / 6 mice 9h after electroporation with the indicated mRNA constructs. The background level of Ea pMHC staining is shown in grey. The graph in the Figure 9C shows the frequency of HA-positive cells detected by intracellular flow cytometry of fresh BMDCs of C57BL / 6 mice 9h after electroporation with the indicated mRNA constructs. Bars indicate median values of two technical replicates.Figure 10 shows the presentation of the MHC-II epitope Ea as percentage of Ea pMHC+ cells, detected by flow cytometry on fresh BMDCs of C57BL / 6 mice 5h, 9h, and 17h after electroporation with the indicated mRNA constructs. Median values of two technical replicates are depicted.Figure 11 shows the in vivo immunogenicity of an LNP-formulated surrogate mRNA vaccine with the optimized fusion protein backbone in C57BL / 6 mice. Naive C57BL / 6 mice were vaccinated intramuscularly with 5pg LNP-formulated B16-CTLA4-E5 (R10667; as depicted in Figure 3) at day 0, 7 and 14. Vaccination with irrelevant mRNA (PpLuc; R8730) served as control. At day 21 , mice were sacrificed and splenocytes were isolated. Splenocytes were restimulated individually with the indicated peptides or DMSO as control and analyzed by flow cytometry. The magnitude of the CD8+ (top) and CD4+ (bottom) T cell responses against the antigenicpeptides is shown as percentage of IFN-Y+ TNF+ cells of CD8+ or CD4+ T cells, respectively. Median values are plotted. The data are representative for two independent experiments. Further details / abbreviations are found in the legend of Figure 3.Figure 12 shows the presentation of the R11047 / CVGBM-encoded HBV-001 peptide on HLA-A*02:01 in HEK293T cells 19h after lipofection with CVGBM. Subsequently, complexes of HBV-001 bound to HLA-A*02:01 were assessed by flow cytometry using an antibody that binds the HBV-001 peptide only when presented on HLA-A*02:01 molecules. Mock transfected (Lipofectamine only) cells and cells pulsed with the HBV-001 peptide served as controls. Bars indicate median values of two technical replicates.Figure 13 shows a graphical overview of the experimental setup of Example 6.2.Figure 14 shows Volcano plots of HLA-I peptides isolated by immunoprecipitation and identified by untargeted LC-MS / MS in cells transfected with CVGBM mRNA. THP-1 cells (top) and HEK293T cells (bottom) were transfected with CVGBM mRNA or control mRNA and lyzed. Peptide / HLA- I complexes were isolated using a pan-HLA class l-specific mAb, separated by HPLC, and analyzed by mass spectrometer (5 technical replicates). For each peptide, the fold change of the area between conditions (X-axis) and the statistical significance of the change (Y-axis) are plotted. CVGBM-encoded peptides are depicted in larger dots and labelled with epitope identifiers. All CVGBM-encoded peptides were only detected in the CVGBM-transfected conditions. Therefore, a sample-specific limit of detection (LOD) was calculated as the median of the five lowest detected areas and used to calculate the fold-change for CVGBM-encoded peptides. The NLDTLMTYV (NLGN4X-001) peptide was present and the most abundant CVGBM-derived HLA-I peptide in all 5 technical replicates of CVGBM-transfected HEK293T and THP-1 cells. However, due to a software issue, it is not shown in the volcano plot of Figure 14A. In a slightly modified re-analysis shown in Figure 14B, however, also NLGN4X-001 could be visualised graphically. The detected CVGBM-encoded peptides in this case are depicted in larger symbols: NLGN4X-001 (square), PTP-005 (downward triangle), PTP-003 (upward triangle) and HBV-001 (diamond).Figure 15 shows the in vivo immunogenicity of LNP-formulated CVGBM in C57BL / 6 mice. Naive C57BL / 6 mice were vaccinated intramuscularly with 5pg LNP-formulated CVGBM (R1 1047) at day 0, 7 and 14. Vaccination with irrelevant mRNA served as control. At day 21 , mice were sacrificed and splenocytes were isolated. Splenocytes were restimulated with pooled peptides covering the CVGBM antigenic peptides or DMSO as control and analyzed by flow cytometry. The magnitude of the CD8+ (Figure 15A) and CD4+ (Figure 15B) T cell responses against the antigenic peptides is shown as percentage of CD8+IFN-y+TNF+CD107a+ or CD4+IFN-y+TNF+ cells of living cells. Median values are plotted.Figure 16 shows the in vivo immunogenicity of LNP-formulated CVGBM in CB6F1 mice. Naive CB6F1 mice were vaccinated intramuscularly with 5pg LNP-formulated CVGBM (R1 1047) at day 0, 6 and 13. Vaccination with irrelevant mRNA served as control. At day 20, mice were sacrificed and splenocytes were isolated. Splenocytes were restimulated with respective peptide pools covering the indicated antigenic peptides PTPRZ1 (27-55), PTPRZ1 (185-213), PTPRZ1 (1337- 1365), BCAN(473-501), BCAN(92-120), BIRC5(90-1 18) or DMSO as control and analyzed by flow cytometry. The magnitude of the CD8+ (top) and CD4+ (bottom) T cell responses against the antigenic peptides is shown as percentage of IFNy+TNF+ cells among CD8 and CD4 T cells, respectively. Median values are plotted.Figure 17 shows a schematic overview of the CV-GBLM-001 trial design. RDE, recommended dose for expansion.Figure 18 shows the schedule of CVGBM administration in the main and optional maintenance treatment period of the CV-GBLM-001 trial. Merely for the sake of clarity, it is stressed that the timelines in the top and bottom are connected. Vertical arrows depict days when CVGBM is administered. Further visits for clinical assessments may optionally occur on day 2, 44, 72, 162, 181 , 351 , 365. DLT, dose-limiting toxicity.Figure 19 shows CVGBM-induced immune responses (% of evaluable patients) in the top and immune responses against individual TAs (% of TA-specific responses) in the bottom. Data cut-off: 23 July 2024; data are preliminary and partially cleaned. Further details are provided in Example 8.7. IR, immune response; NR, non-responder; PBMC, peripheral blood mononuclear cell; TA, tumour antigen.Figure 20 shows the percentage of patients showing an immune response against any, as well as individual, TAAs in three subcategories: CD4+, CD8+, CD8+ or CD4+ T cell responses. Responses were measured by ELISpot assay and analyses were performed on TAAs. For one patient, samples could only be analyzed using Class I and II peptide pools. BCAN, brevican; BIRC5, survivin; HLA, human leukocyte antigen; NLGN4X, neuroligin; PTPRZ, receptor-type tyrosine-protein phosphatase zeta B; TAA, tumor-associated antigen.Figure 21 shows the percentage of patients with an antigen-specific T cell immune response to one or multiple TAAs (n=9); TAA, tumor-associated antigen.Figure 22 shows the maximum antigen-specific T cell responses detected in all responders (n=10). Antigen-specific T cell responses were measured by IFN-y ELISpot assay at baseline (prevaccination) and post-vaccination in samples from all cohorts. Cells were stimulated using HLA- A*02:01 and / or HLA-DR-restricted CD8+ and / or CD4+ T cell epitopes in culture for 7 days and SFC were normalized per million cells. Tumor antigen-derived CD4+ T cell epitopes are shown on the left panel, CD8+ T cell epitopes are shown on the right panel. ELISpot, enzyme-linkedimmunosorbent spot; IVS, in vitro stimulation, PEB, pre-existing boosted immune response; SFC, spot forming cells.Figure 23 shows CVGBM vaccine-induced immune responses at baseline (Day 1) and at pre-determined post-vaccination timepoints. Tumor antigen-specific T cell responses were measured by IFN-y ELISpot using PBMCs at timepoints marked in bold (X-axis). Cells were stimulated using HLA- A*02:01 and / or HLA-DR-restricted CD8+ and / or CD4+ T cell epitopes in culture for 7 days, and SFC were normalized per million cells. Responders are represented by coded patient number (Px) and CVGBM-encoded TAAs (for CD4 and CD8). BCAN, brevican; BIRC5, survivin; ELISpot, enzyme-linked immunosorbent spot; HLA, human leukocyte antigen; IVS, in vitro stimulation; NLGN4X, neuroligin; PBMC, peripheral blood mononuclear cell; PTPRZ, receptortype tyrosine-protein phosphatase zeta B; SFC, spot forming cells.Figure 24 shows secretion of innate immune cytokines in patients from all cohorts (n=16). Volcano plots show the magnitude of change (calculated by mean Iog2 fold change) versus the statistical significance represented by -logio of the Benjamini-Hochberg corrected p-values between the time points for the tested cytokines. Squares above the horizontal line and outside of the vertical lines indicate a statistically significant (<0.05 and |log2FC| >1) increase compared with baseline; squares above the horizontal line and within the vertical lines indicate a statistically significant low magnitude (<0.05 and |log2FC| <1) increase compared with baseline; and squares below the horizontal line and within the vertical lines indicate a non-statistical significance (- 1<log2FC<1) versus baseline. Figure 24 A shows time point Day 2 vs. Day 1 , Figure 24 B shows time point Day 44 vs. Day 43 and Figure C shows time point Day 72 vs. Day 71 . CXCL9, CXC motif chemokine ligand 9; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN, interferon; IL, interleukin; IP, interferon gamma induced protein; MCP, monocyte chemoattractant protein-1 ; TNF, tumor necrosis factor.In the following, Examples illustrating various embodiments and aspects of the invention are presented. However, the present invention shall not to be limited in scope by the specific embodiments presented herein and should rather be understood as being applicable to other compositions or uses as for example defined in the specification. Accordingly, the following preparations and Examples are given to enable those skilled in the art to more clearly understand and to practice the present invention. Indeed, various modifications of the invention in addition to those described herein will become readily apparent to those skilled in the art from the foregoing description, accompanying figures and the Examples below.Example 1 : Preparation of nucleic acids and lipid-based carriersExample 1 illustrates exemplary methods of obtaining nucleic acids of the invention as well as exemplary methods of generating compositions of the invention comprising nucleic acid(s), in particular RNA formulated in lipid-based carriers. Table 1 shows RNA constructs used in the Examples, including theamino acid sequences of the encoded fusion proteins. These RNA constructs / fusion proteins are further depicted in Figures 1 to 3.Table E1: RNA constructs used in the ExamplesExample 1.1. Preparation of DNA templates for RNA in vitro transcriptionDNA sequences encoding the different constructs of the invention were prepared and used for subsequent RNA in vitro transcription reactions. Some DNA sequences were prepared by modifying the wild type or reference encoding DNA sequences by introducing a G / C optimized coding sequence for stabilization and expression optimization. Sequences were introduced into a pUC derived DNA vector to comprise stabilizing heterologous UTR sequences and a stretch of adenosines and an optional histone stem-loop (hSL). The obtained plasmid DNA templates were transformed and propagated in bacteria using common protocols known in the art. Eventually, the plasmid DNA templates were extracted, purified, and linearized using a restriction enzyme.Example 1.2. RNA in vitro transcription from plasmid DNA templatesLinearized DNA templates were used for DNA dependent RNA in vitro transcription (IVT) using T7 RNA polymerase in the presence of a sequence optimized nucleotide mixture (ATP / GTP / CTP / UTP) and cap analog (cap1 : m7G(5’)ppp(5’)(2’OMeA)pG; TriLink) under suitable buffer conditions. Other constructs are produced in the presence of a nucleotide mixture comprising (ATP / GTP / CTP / pseudouridine (ip)) or (ATP / GTP / CTP / N1 -methylpseudouridine (m1 qj)) and a cap analog. After RNA in vitro transcription, the obtained RNA IVT reaction was subjected to purification steps comprising RP-HPLC.Example 1.3. Preparation of lipid-based carriers encapsulating the RNAFor Example 7 to 8, lipid nanoparticles with a formulation as depicted in Table E2 were prepared according to standard procedures in the art.Table E2: Lipid nanoparticle formulation used in Examples 7 and 8The LNP composition used in Example 7 was prepared using the NanoAssemblr microfluidic system (Precision NanoSystems Inc., Vancouver, BC) according to standard protocols which enables controlled, bottom-up, molecular self-assembly of nanoparticles via custom-engineered microfluidic mixing chips that enable millisecond mixing of nanoparticle components at a nanoliter scale.LNP compositions used in Example 7bis and 8 were prepared essentially according to the procedures described in WO2015199952, WO2017004143 and WO2017075531 .Example 2: Selection of suitable target antigens for generation of an mRNA-based multiepitope vaccine candidate against glioblastomaThe aim of the present Example was to select suitable target antigens for generation of an mRNA-based multiepitope vaccine candidate against glioblastoma. During in-depth analyses including but not limited to in silico analyses and preclinical experiments, 8 antigenic peptides from 4 TAAs expressed in Glioblastomas were considered particularly promising for inducing a strong and diversified immune response against GBM tumor cells. The sequences of these eight antigenic peptides and their originating source proteins are depicted in Table E3. Each antigenic peptide had a length of 29aa and comprised the MHC-I / II epitopes as indicated together with flanking regions as in their respective source proteins to allow for correct epitope processing and presentation when encoded by an mRNA vaccine. Notably, in addition to the indicated epitopes, each antigenic peptide was found to comprise multiple other experimentally validated and / or predicted T cell epitopes.Table E3: Particularly preferred GBM antigenic peptides of the inventionExample 2.1. In silico estimations - coverage among Glioblastoma patientsTo estimate the coverage for a vaccine based on these eight particularly preferred antigenic peptides among glioblastoma patients, an internally developed simulation algorithm that integrates epitope / HLA class-l binding information, allele frequency and gene expression in tumors was used.To this end, epitope / HLA class I binding data from the Immune Epitope Database (IEDB) was combined with MHCI epitope predictions using NetMHCPan v4.1 . To generate the predictions, all peptides of lengths between 9 and 11 comprised in the 8 antigenic peptides and the most frequent HLA-A / B / C alleles were considered (HLA-A*01 :01 , HLA-A*02:01 , HLA-A*03:01 , HLA-A*1 1 :01 , HLA-A*24:02, HLA-A*25:01 , HLA- A*26:01 , HLA-A*31 :01 , HLA-A*32:01 , HLA-A*68:01 , HLA-B*07:02, HLA-B*08:01 , HLA-B*13:02, HLA-B*14:02, HLA-B*15:01 , HLA-B*18:01 , HLA-B*27:05, HLA-B*35:01 , HLA-B*35:03, HLA-B*37:01 , HLA-B*38:01 , HLA-B*39:01 , HLA-B*40:01 , HLA-B*40:02, HLA-B*44:02, HLA-B*44:03, HLA-B*49:01 , HLA-B*50:01 , HLA-B*51 :01 , HLA-B*55:01 , HLA-B*56:01 , HLA-B*57:01 , HLA-C*01 :02, HLA-C*02:02, HLA-C*03:03, HLA-C*03:04, HLA-C*04:01 , HLA-C*05:01 , HLA-C*06:02, HLA-C*07:01 , HLA-C*07:02, HLA-C*08:02, HLA-C*12:03).The allele frequency and the gene expression data were obtained from The Cancer Genome Atlas (TCGA) in 155 glioblastoma patients. A gene expression threshold of 10 transcripts per million (TPM) was set to consider a gene expressed in an individual patient’s tumor.The simulation algorithm integrated the different data sources to estimate the patient coverage and its variability; it used NetMHCPan positive predictive values (PPV) to correct for HLA binding prediction errors and avoid over-estimating the coverage.Results:The results are shown in Figure 4 and demonstrate that vaccines based on these eight particularly preferred antigenic peptides have a high coverage among patients with glioblastoma, thus making it a suitable off-the-shelf shared vaccine for this indication. Notably, these results also show that approximately 38% of glioblastoma patients express at least three of the four particularly preferred TAAs and have HLA alleles capable of presenting at least one epitope within at least one antigenic peptide of all of these three TAAs, enabling a diversified immune response in a wide range of glioblastoma patients. Since the coverage estimations were only based on the antigenic peptide sequences and not the full-length TAA sequences, this means the following: i) regarding BCAN this means at least one epitope within BCA-002-long or BCA- 005-long; ii) regarding PTPRZ1 , this means at least one epitope within PTP-003-long, PTP-005-long, PTP- 010-long or PTP-013-long; iii) regarding NLGN4X and BIRC-5, this means at least one epitope within NLGN4X-001-long or BIR-002-long, respectively.Example 2.2. In silico estimations - coverage among Glioblastoma patients with HLA-A*02:01Since multiple epitopes comprised in the 8 antigenic peptides can be presented by HLA-A*02:01 , coverage estimations were additionally performed for patients expressing at least one HLA-A*02:01 allele. To this end, the method described in Example 2.1 was modified accordingly.Results:The results are shown in Figure 5 and demonstrate that vaccines based on these eight particularly preferred antigenic peptides have a remarkably high coverage among glioblastoma with HLA-A*02:01 , thus making it a particularly suitable off-the-shelf shared vaccine for this indication and patient cohort. Notably,these results also show that 95% of glioblastoma patients will express at least three of the four particularly preferred TAAs and have HLA alleles capable of presenting at least one epitope within at least one antigenic peptide of each of these three TAAs, enabling a diversified immune response in a wide range of glioblastoma patients.Example 2.3 Generation of an mRNA -based multiepitope vaccine candidate against glioblastomaThe eight particularly preferred GBM antigenic peptides as well as an antigenic peptide from HBV for monitoring vaccine efficacy were selected for the subsequent generation of an mRNA-based multiepitope vaccine candidate against glioblastoma. The antigenic peptides were encoded as concatenated fusion proteins, in which the 9 antigenic peptides were separated by non-immunogenic G4S linkers and the antigenic peptides from the same TAAs were clustered within the fusion protein (see Figure 1). Those sequences were flanked by additional amino acid sequences to yield an optimized fusion protein backbone for increased peptide presentation and eliciting strong immunogenicity. Those additional sequences comprised the signal peptide and TM / CD from CTLA4, as previously described in WO2019008001 , as well as a C-terminal E5 degron as described in the following Example. The rationale for using such an optimized fusion protein backbone is explained by the findings in Examples 3 to 5. backbone ia C-terminal degron -of fusionIn-depth screenings for modulator elements that can be included in fusion proteins to yield an optimized fusion protein backbone eliciting strong immunogenicity identified the C-terminal E5 degron as promising candidate. Thus, in Examples 3 to 5, such an optimized fusion protein backbone including a C-terminal E5 degron was assessed in detail with regard to fusion protein quantity (Example 3) and epitope presentation (Example 4) upon transfection as well as in vivo immunogenicity (Example 5). To this end, various surrogate mRNA constructs allowing for the analyses of these aspects were used (see Figures 2 and 3 and description below).The aim of the present Example was to comparatively analyze the intracellular protein quantity of fusion proteins with or without C-terminal E5 degron upon mRNA transfection. To this end, various surrogate mRNA constructs encoding for the GBM / HBVc antigenic peptides as well as a reporter module as depicted in Figure 2 were used. This reporter module comprises an 3xHA-tag, which allows for detection of the fusion protein by intracellular flow cytometry. RNA R11044 (negative control) encodes for a fusion protein comprising the same GBM / HBVc antigenic peptides as R11052 / R11053, but lacking the reporter module, CTLA4 sequences and degron. Transfection experiments with three cell types were performed: fresh murine bone-marrow derived dendritic cells (BMDCs) from C57BL / 6 mice; JAWSII cells (immortalized immature dendritic cell line established from the bone marrow of C57BL / 6 mice); HeLa cells.Culture and transfection of fresh murine BMDCs:Fresh murine BMDCs were generated using standard protocols. Briefly, bone marrow cells were harvested from the tibias and femurs of C57BL / 6 mice and cultured at 1x10e6 cells / ml with complete RPMI medium (RPMI Gibco 52400-025, 10% FCS, 1 % P / S, 4mM L-Glutamine) with GM-CSF (20ng / ml, Miltenyi 130-095-793) and IL-4 (5ng / ml, Miltenyi 130-097-757) in a 6-well plate. After 3 days, the same volume of complete RPMI medium with GM-CSF (20ng / ml) and IL-4 (5ng / ml) was added. At day 6, BMDCs were harvested and resuspended in Opti-MEM (Gibco 31985-070) medium on ice. 3x10e6 cells in 200pl Opti-MEM medium were mixed with 20pg mRNA (in 30pl), transferred to a 2mm gap sterile disposable electroporation cuvette and immediately electroporated using a Gene Pulser Xcell electroporation system (Bio-Rad; Square wave, 300V, 1 pulse of 6ms). After electroporation, 770p I warm complete RPMI medium were added to the cuvette and cells were transferred to a well of a 6-well plate containing 1 ml warm complete RPMI medium with a final concentration of 0.1 pg / ml LPS (Sigma-Aldrich L6529). 9h post-transfection, cells were harvested and analyzed by intracellular flow cytometry as described below.Culture and transfection of JAWSII cells:On day 0, JAWSII cells were seeded at a density of 500 000 cells / well in a 24-well plate in standard media for this cell line (Alpha MEM with nucleosides 12571 -063 Gibco, 20%FCS, 1 %P / S, 4mM L-Glutamine, 1 mM sodium pyruvate and 5ng / ml GM-CSF). On day 1 , cells were transfected with 3pg / well of Lipofectamine- formulated RNA R11052, R11053 or R1 1044 according to standard protocols (Lipofectamine 2000; Invitrogen; #11668-019; RNA:Lipofectamine = 1 pg:2pl). On day 2, 24h post-transfection, cells were harvested and analyzed by intracellular flow cytometry as described below.Culture and transfection of HeLa cells:On day 0, HeLa cells were seeded at a density of 400 000 cells / well in a 6-well plate. On day 1 , cells were transfected with 1 pg / well of lipofectamine-formulated RNA R11052, R11053 or R11044 according to standard protocols (Lipofectamine 2000; Invitrogen; #11668-019; RNA:Lipofectamine = 1 pg:2pl). On day 2, 24h post-transfection, cells were harvested and analyzed by intracellular flow cytometry as described below.Flow cytometry:Cells were intracellularly stained with an anti-HA.11 epitope tag antibody (clone 16B12; BioLegend #901524) and subsequently analyzed on a flow cytometer.Results:The results are shown in Figure 6 (fresh murine BMDC), Figure 7 (JAWSII cells) and Figure 8 (HeLa cells). The results for all three cell types show the highly surprising pattern that an increased signal for the HA-tag was detected for the fusion protein comprising the C-terminal E5 degron compared to the corresponding fusion protein without degron. This suggests that increased amounts of the fusion protein with the C-terminal E5 degron are present.Example 4: Optimized fusion protein backbone including a C-terminal degron - epitope presentation The aim of the present Example was to comparatively analyze the MHC-I and MHC-II presentation of peptides derived from mRNA-encoded fusion proteins with or without C-terminal E5 degron. Due to the lack of antibodies detecting the GBM peptides when presented by MHC molecules, again the mRNA surrogate constructs encoding for the GBM / HBVc antigenic peptides as well as a reporter module as depicted inFigure 2 were used. This reporter module comprises two antigenic peptides from chicken ovalbumin (SERPINB14, aa 247-275 comprising the MHC-I epitope SIINFEKL) and murine H2-Ea (aa 71-99 comprising the MHC-II epitope Ea aa 52-68), for which detection antibodies were available. SIINFEKL and Ea are two peptides that can be presented on MHC class I and class II molecules of C57BL / 6 mice, respectively, and can be detected as peptide-MHC complexes by specific antibodies. This allows to analyze the processing, loading and presentation of MHC-I / II of peptides derived from mRNA-encoded fusion proteins.Fresh murine BMDCs from C57BL / 6 mice were used in the present Example. Fresh BMDCs were generated, cultured and electroporated as described in Example 3. Besides R11052 / R11053 / R11044, further comparator mRNAs as described below were used.R11055 (GBMr - comparator 1) encodes for a fusion protein comprising the same GBM / HBVc antigenic peptides and reporter module as R11052 / R11053, but lacking the CTLA4 sequences and degron. Consequently, this fusion protein should localize to the cytosol.R11063 (GBMr - comparator 2) encodes for a fusion protein comprising the same GBM / HBVc antigenic peptides and reporter module as R11052 / R1 1053, but lacking the CTLA4 sequences and degron, and comprising at the N-terminus a signal peptide and further amino acid sequences derived from LAMP1 intended to localize the fusion protein to the inside of lysosomes and late endosomes.R11061 (GBMr - comparator 3) encodes for a fusion protein comprising the same GBM / HBVc antigenic peptides and reporter module as R11052 / R1 1053, but lacking the CTLA4 sequences and degron, and comprising at the N-terminus a signal peptide (derived from a protein other than CTLA4 and LAMP1) intended to localize the fusion protein to the endoplasmic reticulum.All of those comparator mRNAs had the same mRNA backbone as R11052 / R11053, e.g. same cap, UTRs, hSL-A100.9h post transfection, the BMDCs were extracellularly stained for the SIINFEKL peptide presented on MHC- I (anti-mouse H-2Kb bound to SIINFEKL antibody; clone 25-D1.16; BioLegend #141612) and the Ea peptide presented on MHC-II molecules (anti-MHC class II Y-Ae; Santa Cruz #sc32247). Furthermore, cells were intracellularly stained with an anti-HA.11 epitope tag antibody (clone 16B12; BioLegend #901524) and subsequently analyzed on a flow cytometer. Additionally, for R11044 / R11053 / R11055 / R11063 a time kinetic of MHC-II peptide presentation was carried out, with flow cytometric readouts at 5h, 9h and 17h after transfection.Results:The results are shown in Figure 9 and 10. Without wishing to be bound by any theory, the results can be described and interpreted as follows. Staining for SIINFEKL / MHC-I complexes detected similar amounts of the MHC-I presented peptide on cells transfected with R11053 (construct with degron) and R1 1052(construct without degron) in this experimental setup (Figure 9A). In contrast, staining for Ea / MHC-ll complexes surprisingly detected increased levels of the MHC-II presented peptide on cells transfected with R11053 compared to cells transfected with R11052 (Figure 9B). Simultaneous quantification of the HA-tag (as surrogate for intracellular fusion protein quantity) furthermore confirmed that the increased MHC-II peptide presentation is not simply caused by the increased protein amount of the R11053 fusion protein, since R11061 (construct with alternative SP) showed high intracellular protein amounts, but no (=background level) MHC-II peptide presentation (Figure 9C).Furthermore, the comparative analyses revealed that R11055 (construct without CTLA4 sequences and degron) showed no MHC-II peptide presentation, while R11063 (construct with LAMP1 sequences) showed high MHC-II peptide presentation. This observation is consistent with the accepted theory that presentation of MHC-II epitopes requires the processing of proteins localized to endosomal-lysosomal vesicles. Indeed, R11063 (constructs with LAMP1 sequences intended to localize the fusion protein to the inside of lysosomal and late-endosomal vesicles) shows a high level of MHC-II epitope presentation, while R1 1055 (construct without CTLA4 sequences and degron intended to localize to the cytosol) shows none. R11052 (construct with CTLA4 sequences, but without degron) shows some degree of MHC-II presentation, which is in line with literature that describes CTLA4 as a “fast recycling” protein that is readily and recurrently internalized to enter the endosomal-lysosomal compartments. Unexpectedly, however, the fusion of the C-terminal E5 degron with the C-terminus of CTLA4 further increased MHC-II peptide presentation, even to levels slightly higher than those observed with R11063. Moreover, high MHC-II peptide presentation persisted for a longer period of time than with R11063 (Figure 10). This may suggest that the C-terminal E5 degron prolongs the retention time of immunogenic fusion proteins in endosomal-lysosomal vesicles.In summary, these data demonstrate that epitopes within fusion proteins based on the optimized CTLA4- E5 backbone are correctly cleaved and released from the context of their fusion protein (thus processed similarly as in their natural source proteins), and loaded onto MHC-I and MHC-II molecules. Unexpectedly in this context, the addition of the C-terminal E5 degron promotes enhanced and long-lasting MHC-II peptide presentation. In contrast, fusion proteins localized to the cytosol (R11055) or inside the endoplasmic reticulum (R1 1061) only enable efficient MHC-I peptide presentation. fusion protein backbone ia C-terminal degron - in vivoThe aim of the experiment was to assess the in vivo immunogenicity of a cancer vaccine based on the optimized fusion protein backbone in a proof-of-concept mouse study. To this end, the immunogenicity of an LNP-formulated mRNA vaccine with this optimized fusion protein backbone encoding antigenic peptides derived from the B16.F10 melanoma cell line was tested in C57BL / 6 mice. The structural overview of this mRNA vaccine (B16-CTLA4-E5 mRNA; R10667) is given in Figure 3; further details regarding the encoded antigenic peptides are given in Table E4.In brief, female 7-9 week old C57BL / 6 mice were vaccinated intramuscularly with 5pg LNP-formulated B16- CTLA4-E5 (R10667) or PpLuc control (R8730) mRNA at day 0, 7 and 14 (n=5 / group). At day 21 , mice weresacrificed and splenocytes were isolated. Splenocytes were restimulated with 5pg / ml of the individual peptides of Table E4 or DMSO as control for 6 hours with the addition of GolgiPlug (BD Biosciences) after 1 h. Splenocytes were then stained with fluorophore-conjugated antibodies recognizing surface and intracellular markers and analysed by flow cytometry to determine CD8 responses (IFN-gamma / TNF-alpha double positive population of CD8 T cells) and CD4 responses (IFN-gamma / TNF-alpha double-positive population of CD4 T cells) against the antigenic peptides.Table E4: Antigenic peptides encoded by B16-CTLA4-E5 mRNA (R10667) and used for re-stimulationResults:The results are shown in Figure 11 . B16-CTLA4-E5 showed potent CD8 and CD4 T cell responses. Overall, the data demonstrate that mRNA vaccines based on the optimized fusion protein backbone induce potent CD8 and CD4 T-cell responses against the encoded antigenic peptides. Notably, this holds true for a variety of different antigen classes, e.g. forTAAs, neoepitopes and synthetic epitopes as well as for both unmutated and mutated epitopes. The optimized fusion protein backbone is thus able to raise potent immune responses against a variety of different target antigens.Example 6: Presentation of peptides derived from the CVGBM fusion protein on MHC moleculesThe findings in Examples 2 to 5 were the basis for generation of an mRNA-based multiepitope vaccine candidate against glioblastoma, R11047 / CVGBM, for further preclinical and clinical testing.Whereas the experimental setups in Examples 3 to 5 required surrogate mRNA constructs, further experimental methods were used in Example 6 and 7 in order to directly characterize the clinical candidate mRNA R11047 / CVGBM prior to clinical evaluation.The aim of the present Example was to determine whether upon CVGBM mRNA transfection the encoded fusion protein is correctly translated and processed and whether the encoded peptides are presented on MHC / HLA molecules of human cells.To this end, two experimental readouts, flow cytometry and mass-spectrometry, were used.The availability of a TCR-like antibody that detects the peptide HBV-001 when bound to HLA-A*02 allowed the analysis of the presentation of this CVGBM-encoded peptide on cells transfected with CVGBM mRNA. To this end, CVGBM mRNA was transfected into HEK293T cells, which endogenously express the HLA- A*02:01 allele capable of presenting HBV-001 , and complexes of HBV-001 bound to HLA-A*02:01 were assessed by flow cytometry.In brief, on day 0, HEK293T cells were seeded at 500.000 cells / well in 6-well plates. On day 1 , cells were transfected with 5pg of Lipofectamine-formulated CVGBM or mock-transfected with the same amount of lipofectamine according to standard protocols (Lipofectamine 2000; Invitrogen; #1 1668-019; RNA:Lipofectamine = 1 pg:2pl). On day 2, 19h post transfection, cells were stained with an TCR-like antibody that binds the HBV-001 peptide only when presented on HLA-A*02:01 molecules (clone c18 / A2; creative biolabs #TCR-LA-ZP059; 1 pg / ml) and assessed by flow cytometry. HEK293T cells pulsed with 10pg / ml of HBV-001 peptide for 2h served as staining control.Results:The results are shown in Figure 12. HEK293T cells transfected with CVGBM mRNA showed a strong staining for HBV-001 :HLA-A*02:01 complexes. This confirmed the proper translation and processing of the encoded CVGBM fusion protein and subsequent efficient loading of resulting peptides on MHC molecules.Example 6.2: Mass-spectrometrv analysesThe aim of the experiment was to further confirm the correct translation and processing of the CVGBM fusion protein and the loading and presentation of resulting processed peptides on MHC / HLA in human cells, in particular to confirm the presentation of the encoded GBM peptides. To this end, cells were transfected with CVGBM mRNA and MHC-I presented peptides were isolated by immunoprecipitation and identified by untargeted LC-MS / MS (experimental setup shown in Figure 13).Since for mass spectrometry analyses large amounts of transfected cells are needed, model cell lines were used: THP-1 and HEK293T cells both endogenously expressing HLA-A*02:01 . In brief, on day 0, HEK293T or THP-1 cells were seeded in cell culture dishes (0 = 15cm; 6.4x106HEK293T or 8x106THP-1 cells per dish; 16 dishes per cell line). On day 1 , cells were transfected with 32pg RNA per dish of Lipofectamine- formulated CVGBM / R11047 or control mRNA according to standard protocols (Lipofectamine 2000; Invitrogen; #11668-019; RNA:Lipofectamine = 1 pg:2pl). The control mRNA encoded for a completely different fusion protein that had no overlapping amino acid sequence besides the linker sequence. After 6h, cells were harvested by pipetting or scraping, washed twice in ice-cold PBS, and snap-frozen at -80°C as dry pellets, with 8 dishes pooled per cell line and RNA.Subsequently, MHC-I presented peptides were isolated by immunoprecipitation and identified by untargeted LC-MS / MS as follows:1. Isolation of HLA ligands:HLA class I molecules were isolated using standard immunoaffinity purification, using the pan-HLA class I- specific mAb W6 / 32 (produced in-house) to extract HLA ligands.2. Analysis of HLA ligands by LC-MS / MS:HLA ligand extracts were analyzed in five technical replicates. In brief, peptide samples were separated by nanoflow high-performance liquid chromatography (RSLCnano, Thermo Fisher Scientific) using a 50pm x 25cm PepMap rapid separation liquid chromatography column (Thermo Fisher Scientific) and a gradient ranging from 2.4% to 32.0% acetonitrile over the course of 90min. Eluting peptides were analyzed in an online-coupled LTQ Orbitrap Fusion Lumos mass spectrometer (Thermo Fisher Scientific) using a top speed collision-induced dissociation fragmentation method.3. Database search and HLA annotation:The SEQUEST HT search engine (University of Washington) was used to search the human proteome as comprised in the Swiss-Prot database (20,279 reviewed protein sequences, September 27th 2013 with the R11047 sequence added) without enzymatic restriction. Precursor mass tolerance was set to 5ppm, and fragment mass tolerance to 0.02Da. Oxidized methionine was allowed as a dynamic modification. The false discovery rate (FDR) was estimated using the Percolator algorithm and limited to 5%. Peptide lengths were limited to 8-12 amino acids. HLA class I annotation was performed using NetMHCpan 4.1 and SYFPEITHI annotating peptides with scores or percentile rank below 2% or higher than 60, respectively.4. Label-free quantitation of HLA ligand presentation:LC-MS / MS analysis was performed in five technical replicates for each sample. Relative quantification of HLA ligands was performed based on the area of the corresponding precursor extracted ion chromatograms using ProteomeDiscoverer 1.4.1.14 (Thermo Fisher Scientific). High-quality peptide spectrum matches filtered for 5% FDR and subsequently screened for predicted HLA were used to generate seed lists for semi-quantitative volcano plot analysis. The sequences from these seed lists were then queried across all runs without applying any filtering for spectral quality criteria (XCorr, FDR) to extract areas for IDs not passing these thresholds. For Volcano plot analysis, peptides only found in one technical replicate were discarded and the sample-specific limit of detection (LOD) was calculated as the median of the five lowest areas and inserted for missing areas to allow for fold-change calculation of HLA ligands detected in only one of both conditions. Technical replicates as well as experiments / conditions were normalized based on the summed intensities of all identified precursors in each MS run. Subsequently, the ratios of the mean areas of the individual peptides in the five LFQ-MS runs of each sample were calculated and unpaired, heteroskedastic two-tailed t-tests implementing Benjamini-Hochberg correction were performed using an in-house R script (v3.2.3).Results:A high-level summary of the detected MHC-I peptides is shown in Table E5.#5% false discovery rate (FDR) was applied to reduce number of peptides.+Remaining peptides were filtered by Syfpeithi score >60% and / or NetMHC rank <2.0.* Same results with and without Syfpeithi / NetMHC filter.3 and 4 MHC-I peptides originating from the CVGBM fusion protein could be detected in THP1 and HEK293T cells, respectively, which is shown in Table E6. All of these peptides were identified in all 5 technical replicates (runs) of each sample.Table E6: Summary of detected MHC-I peptides derived from CVGBM fusion proteinStatistical analysis was performed as follows and is graphically depicted by the Volcano plots shown in Figure 14. 5 technical replicate LC-MS measurements were acquired per condition which allows statistical analysis. For each peptide in the two conditions compared (R11047 and control mRNA), the fold change of the area between conditions was calculated using a sample-specific limit of detection (LOD) if the peptide was only present in one condition. Due to the fact that 5 technical replicates for each condition were acquired, and peptides should / could be present in all replicates with a similar area, a statistical test can be performed: in this case a two tailed t-test corrected after Benjamini Hochberg for multiple testing. The resulting statistics are depicted in the volcano plots of Figure 14, which have to be interpreted as follows: y-axis shows log 10 of corrected p-value, which corresponds to significance of up / down modulation x-axis shows Iog2 of fold change of condition 1 compared to condition 2 (the Iog2 is used to represent the data symmetrically)upper left and upper right area represent individual peptide areas that were up / down modulated with a p-value <0.00...

Claims

Claims1. An artificial nucleic acid comprising at least one coding sequence, wherein the at least one coding sequence encodes at least one polypeptide or protein, the at least one polypeptide or protein comprising at least one antigenic peptide or protein from each of the tumour-associated antigens (TAA)- Brevican core protein (BCAN), or a variant thereof,- Neuroligin-4, X-linked (NLGNX4), or a variant thereof,- Receptor-type tyrosine-protein phosphatase zeta (PTPRZ1), or a variant thereof, and- Baculoviral IAP repeat-containing protein 5 (BIRC5), or a variant thereof.

2. The artificial nucleic acid of claim 1 , wherein the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein from the TAA Elongation of very long chain fatty acids protein 2 (ELOVL2) or from a variant thereof.

3. The artificial nucleic acid of claim 1 or 2, wherein the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein comprising or consisting of an amino acid sequence according to- SEQ ID NO: 124 (BCAN), or an immunogenic fragment or variant thereof,- SEQ ID NO: 125 (NLGNX4), or an immunogenic fragment or variant thereof, - SEQ ID NO: 126 (PTPRZ1), or an immunogenic fragment or variant thereof, and / or- SEQ ID NO: 127 (BIRC5), or an immunogenic fragment or variant thereof.

4. The artificial nucleic acid of claim 3, wherein the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein comprising or consisting of an amino acid sequence according to SEQ ID NO: 128 (ELOVL2) or an immunogenic fragment or variant thereof.

5. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 antigenic peptides from at least one of the TAAs BCAN, NLGNX4, PTPRZ1 , BIRC5 or ELOVL2, or from a variant thereof, preferably at least 4 antigenic peptides from PTPRZ1 or from a variant thereof and / or at least 2 antigenic peptides from BCAN or from a variant thereof.

6. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein comprising or consisting of at least one T-cell epitope.

7. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein comprising or consisting of at least one T-cell epitope, wherein the at least one antigenic peptide or protein is from each of- BCAN or a variant thereof,- NLGNX4 or a variant thereof,- PTPRZ1 or a variant thereof, and- BIRC5 or a variant thereof.

8. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein comprising or consisting of at least one T-cell epitope, wherein the at least one antigenic peptide or protein is from ELOVL2 or from a variant thereof.

9. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein comprising or consisting of at least one major histocompatibility complex class I (MHC-I) epitope.

10. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein comprising or consisting of at least one MHC-I epitope, wherein the at least one antigenic peptide or protein is from each of- BCAN or a variant thereof,- NLGNX4 or a variant thereof, and- PTPRZ1 or a variant thereof.

11. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises at least three antigenic peptides, each of the at least three antigenic peptides comprising or consisting of at least one MHC-I epitope from PTPRZ1 or from a variant thereof.

12. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein comprising or consisting of at least one MHC-I epitope from ELOVL2 or from a variant thereof.

13. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein, the at least one antigenic peptide or protein comprising or consisting of an amino acid sequence according to- SEQ ID NO: 130 (BCA-002) or an immunogenic fragment or variant thereof,- SEQ ID NO: 132 (NLGN4X-001) or an immunogenic fragment or variant thereof,- SEQ ID NO: 133 (PTP-003) or an immunogenic fragment or variant thereof,- SEQ ID NO: 134 (PTP-005) or an immunogenic fragment or variant thereof, and / or- SEQ ID NO: 136 (PTP-013) or an immunogenic fragment or variant thereof.

14. The artificial nucleic acid of claim 13, wherein the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein comprising or consisting of the amino acid sequence according to SEQ ID NO: 138 (ELGVL2-001) or an immunogenic fragment or variant thereof.

15. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein comprising or consisting of at least one major histocompatibility complex class II (MHC-I I) epitope.

16. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein comprising or consisting of at least one MHC-II epitope, wherein the at least one antigenic peptide or protein is from each of- BIRC-5 or a variant thereof, and- PTPRZ1 or a variant thereof, and optionally from- BCAN or a variant thereof.

17. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein, the at least one antigenic peptide or protein comprising or consisting of an amino acid sequence according to- SEQ ID NO: 137 (BIR-002) or an immunogenic fragment or variant thereof,- SEQ ID NO: 135 (PTP-010) or an immunogenic fragment or variant thereof, and / or- SEQ ID NO: 131 (BCA-005) or an immunogenic fragment or variant thereof.

18. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein, the at least one antigenic peptide or protein comprising or consisting of the amino acid sequences according to- SEQ ID NO: 130 (BCA-002) or an immunogenic fragment or variant thereof,- SEQ ID NO: 132 (NLGN4X-001) or an immunogenic fragment or variant thereof,- SEQ ID NO: 133 (PTP-003) or an immunogenic fragment or variant thereof,- SEQ ID NO: 134 (PTP-005) or an immunogenic fragment or variant thereof,- SEQ ID NO: 136 (PTP-013) or an immunogenic fragment or variant thereof,- SEQ ID NO: 137 (BIR-002) or an immunogenic fragment or variant thereof, and- SEQ ID NO: 135 (PTP-010) or an immunogenic fragment or variant thereof, and optionally- SEQ ID NO: 131 (BCA-005) or an immunogenic fragment or variant thereof.

19. The artificial nucleic acid of claim 18, wherein the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein comprising or consisting of the amino acid sequence according to SEQ ID NO: 138 (ELOVL2-001) or an immunogenic fragment or variant thereof.

20. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein from a viral antigen, or from a variant thereof, preferably from Hepatitis B virus (HBV) core antigen or from a variant thereof.

21. The artificial nucleic acid of claim 20, wherein the at least one antigenic peptide or protein from the viral antigen comprises or consists of at least one MHC-I and / or MHC-II epitope, preferably wherein the at least one antigenic peptide or protein comprises or consists of the amino acid sequence SEQ ID NO: 139 (HBV-001) or an immunogenic fragment or variant thereof.

22. The artificial nucleic acid of any one of the preceding claims, wherein the at least one antigenic peptide consists of about 6-500 amino acids, preferably of about 20, 21 , 22, 23, 24, 25, 26, 27, 29, 30, 31 , 32, 33, 34, or 35 amino acids, more preferably of 29 amino acids.

23. The artificial nucleic acid of any one of the preceding claims, wherein the at least one antigenic peptide comprises at least one MHC-I and / or MHC-II epitope, preferably as specified in any one of claims 13 to 21 , wherein the at least one MHC-I and / or MHC-II epitope in the antigenic peptide is flanked N- and C-terminally by amino acid sequences occurring in the respective wild type protein or ina variant thereof, wherein the lengths of the amino acid sequences flanking the at least one MHC-I and / or MHC-II epitope N- or C-terminally, respectively, comprise at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, or 40 amino acid residues.

24. The artificial nucleic acid of any one of claim 23, wherein the lengths of the amino acid sequences flanking the at least one MHC-I and / or MHC-II epitope N- or C-terminally, respectively, differ from each other by not more than 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19 or 20 amino acid residues, preferably wherein the lengths of the amino acid sequences flanking the at least one MHC-I and / or MHC-II epitope N- or C-terminally are identical.

25. The artificial nucleic acid of any one of claim 23 or 24, wherein the lengths of the amino acid sequences flanking the at least one MHC-I and / or MHC-II epitope N- or C-terminally comprise at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid residues.

26. The artificial nucleic acid of any one of claims 23 to 25, wherein the N- and C-terminally flanking amino acid sequences allow the inclusion of MHC-I and / or MHC-II epitopes other than amino acid sequences as specified in any one of claims 13 to 21 or any other MHC-I and / or MHC-II epitope comprised in any of these sequences.

27. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein, the at least one antigenic peptide or protein comprising or consisting of an amino acid sequence according to- SEQ ID NO: 143 (BCA-002-long), or an immunogenic fragment or variant thereof, - SEQ ID NO: 145 (NLGN4X-001-long), or an immunogenic fragment or variant thereof, - SEQ ID NO: 146 (PTP-003-long), or an immunogenic fragment or variant thereof, - SEQ ID NO: 147 (PTP-005-long), or an immunogenic fragment or variant thereof, - SEQ ID NO: 149 (PTP-013-long), or an immunogenic fragment or variant thereof, - SEQ ID NO: 150 (BIR-002-long), or an immunogenic fragment or variant thereof, - SEQ ID NO: 148 (PTP-010-long), or an immunogenic fragment or variant thereof,- SEQ ID NO: 144 (BCA-005-long), or an immunogenic fragment or variant thereof, and / or- SEQ ID NO: 152 (HBV-001-long), or an immunogenic fragment or variant thereof, preferably, wherein the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein, the at least one antigenic peptide or protein comprising or consisting of the amino acid sequences according to- SEQ ID NO: 143 (BCA-002-long), or an immunogenic fragment or variant thereof, and - SEQ ID NO: 145 (NLGN4X-001-long), or an immunogenic fragment or variant thereof, and - SEQ ID NO: 146 (PTP-003-long), or an immunogenic fragment or variant thereof, and - SEQ ID NO: 147 (PTP-005-long), or an immunogenic fragment or variant thereof, and - SEQ ID NO: 149 (PTP-013-long), or an immunogenic fragment or variant thereof, and - SEQ ID NO: 150 (BIR-002-long), or an immunogenic fragment or variant thereof, and- SEQ ID NO: 148 (PTP-010-long), or an immunogenic fragment or variant thereof, and, optionally- SEQ ID NO: 144 (BCA-005-long), or an immunogenic fragment or variant thereof, and / or- SEQ ID NO: 152 (HBV-001-long), or an immunogenic fragment or variant thereof.

28. The artificial nucleic acid of claim 27, wherein the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein comprising or consisting of the amino acid sequence according to SEQ ID NO: 151 (ELOVL2-001-long), or an immunogenic fragment or variant thereof.

29. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 antigenic peptides from at least one of the TAAs BCAN, NLGNX4, PTPRZ1 , BIRC5 or ELOVL2, or from a variant thereof, wherein the at least 2, 3, 4, 5, 6, 7, 8, 9, or 10, preferably all, antigenic peptides from the same TAA or from the same variant of a TAA are comprised in one encoded polypeptide or protein.

30. The artificial nucleic acid of claim 29, wherein the at least 2, 3, 4, 5, 6, 7, 8, 9, or 10, preferably all antigenic peptides from the same TAA or from the same variant of a TAA are clustered within the one encoded polypeptide or protein.

31. The artificial nucleic acid of claims 29 or 30, wherein the at least one encoded polypeptide or protein comprises at least one antigenic peptide comprising or consisting of at least one MHC-II epitope and at least one antigenic peptide comprising or consisting of at least one MHC-I epitope from the same TAA or from the same variant of a TAA, wherein the at least one antigenic peptide comprising or consisting of at least one MHC-II epitope is located N-terminally of the at least one antigenic peptide comprising or consisting of at least one MHC-I epitope.

32. The artificial nucleic acid of claim 31 , wherein the amino acid sequence according to SEQ ID NO: 131 (BCA-005) is located N-terminally of the amino acid sequence according to SEQ ID NO: 130 (BCA- 002), and / or the amino acid sequence according to SEQ ID NO: 135 (PTP-010) is located N-terminally of the amino acid sequence according to SEQ ID NO: 133 (PTP-003), SEQ ID NO: 134 (PTP-005) and / or SEQ ID NO: 136 (PTP-013).

33. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises at least one linker element, preferably a G4S linker element, wherein the at least one linker element is an amino acid sequence located between two antigenic peptides or proteins, preferably between two antigenic peptides or proteins as defined in any one of the preceding claims, or located between an antigenic peptide or protein and an additional amino acid sequence as defined in any one of the preceding claims, or located between two additional amino acid sequences as defined in any one of the preceding claims.

34. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises at least one additional amino acid sequence selected from an immune response activating signal transduction protein located in the external plasma membrane (IRSTepm) or from a variant thereof, preferably wherein this at least one additional amino acid sequence from an IRSTepm or from a variant thereof is located C-terminally of the most C-terminal antigenic peptide or protein, or of a linker element fused C-terminally to said antigenic peptide or protein.

35. The artificial nucleic acid of claim 34, wherein the at least one additional amino acid sequence selected from an IRSTepm or from a variant thereof is an amino acid sequence from CTLA4 or from a variantthereof, preferably the amino acid sequence according to SEQ ID NO: 201, or a fragment or variant thereof.

36. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises at least one additional amino acid sequence selected from a signal peptide or from a variant thereof, preferably wherein the at least one additional amino acid sequence from a signal peptide or from a variant thereof is located N-terminally of the most N-terminal antigenic peptide or protein, or N-terminally of a linker element fused N-terminally to said antigenic peptide or protein.

37. The artificial nucleic acid of claim 36, wherein the at least one additional amino acid sequence selected from a signal peptide or from a variant thereof is from CTLA4 or from a variant thereof, preferably SEQ ID NO: 198 or SEQ ID NO: 199 or SEQ ID NO: 200 or a fragment or variant of any of these.

38. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises at least one amino acid sequence from a modulator element, wherein the modulator element modulates / impacts the- expression / translation of, and / or- production of, and / or- folding of, and / or- stability of, and / or- degradation of, and / or- the intracellular protein amount of, and / or- turnover of, and / or- processing for presentation by MHC-I and / or MHC-II molecules of, and / or- retention time in endosomal-lysosomal vesicles of, and / or- loading of MHC-I and / or MHC-II molecules, and / or- epitope presentation on MHC-I and / or MHC-II molecules, of the at least one encoded polypeptide or protein upon artificial nucleic acid administration, preferably wherein the modulator element is a heterologous element.

39. The artificial nucleic acid of claim 38, wherein the modulator element is a degron.

40. The artificial nucleic acid of any claim 38 or 39, wherein the modulator element is a ubiquitindependent degron.

41. The artificial nuclei acid of any one of claims 38 to 40, wherein the modulator element, preferably a degron, comprises at least one recognition site for an E3 ubiquitin ligase, preferably for a Cullin-RING E3 type ubiquitin ligase, most preferably for a CuM00^12Cullin-RING type E3 ubiquitin ligase.

42. The artificial nucleic acid of any one of claims 38 to 41 , wherein the modulator element, preferably a degron, is located at the N-terminus of, at the C-terminus of, or within the amino acid sequence of the at least one encoded polypeptide or protein.

43. The artificial nucleic acid of any one of claims 38 to 42, wherein the degron comprises or consists of an amino acid sequence- of at least 2, 3, 4, or 5, preferably of 5 glutamic acids and is preferably located at the C-terminus of the at least one encoded polypeptide or protein,- of at least 2, 3, 4, or 5, preferably of 5 glycines, and is preferably located at the C-terminus of the at least one encoded polypeptide or protein,- of at least 2, 3, 4, or 5, preferably of 5 arginines, and is preferably located at the N- or C-terminus of the at least one encoded polypeptide or protein, or- of at least 2, 3, 4, or 5, preferably of 5 lysines, and is preferably located at the N-terminus of the at least one encoded polypeptide or protein.

44. The artificial nucleic acid of any one of claims 38 to 41 and 43, wherein the modulator element, preferably a degron, more preferably a degron as defined in any one of claims 38 to 41 and 43, most preferably a degron comprising or consisting of an amino acid sequence of at least 2, 3, 4, or 5 glutamic acids is located C-terminally of an additional amino acid sequence selected from an IRSTepm, preferably located C-terminally of an additional amino acid sequence from an IRSTepm as defined in claim 35.

45. The artificial nucleic acid of any one of claims 38 to 44, wherein the at least one encoded polypeptide or protein comprising the modulator element, preferably a degron, is characterized by an increased intracellular protein amount upon artificial nucleic acid administration compared to a corresponding polypeptide or protein without the modulator element.

46. The artificial nucleic acid of any one of claims 38 to 45, wherein the at least one encoded polypeptide or protein comprising the modulator element, preferably a degron, is characterized by an increased presentation of at least one MHC-II epitope comprised in the at least one encoded polypeptide or protein upon artificial nucleic acid administration compared to a corresponding polypeptide or protein without the modulator element.

47. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises or consists of an amino acid sequence according to- SEQ ID NO: 156 or an immunogenic fragment or variant thereof,- SEQ ID NO: 157 or an immunogenic fragment or variant thereof,- SEQ ID NO: 158 or an immunogenic fragment or variant thereof,- SEQ ID NO: 159 or an immunogenic fragment or variant thereof,- SEQ ID NO: 160 or an immunogenic fragment or variant thereof,- SEQ ID NO: 161 or an immunogenic fragment or variant thereof,- SEQ ID NO: 162 or an immunogenic fragment or variant thereof, or- SEQ ID NO: 163 or an immunogenic fragment or variant thereof.

48. The artificial nucleic acid of claim 47, wherein the at least one encoded polypeptide or protein comprises or consists of the amino acid sequence according to SEQ ID NOs: 157 or 163, or of an immunogenic fragment or variant of any of these sequences, preferably wherein the immunogenic fragment or variant comprises or consists of an amino acid sequence being at least 70%, 80%, 85%,86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 157 or 163.

49. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises or consists of an amino acid sequence according to- SEQ ID NO: 172 or an immunogenic fragment or variant thereof,- SEQ ID NO: 173 or an immunogenic fragment or variant thereof,- SEQ ID NO: 174 or an immunogenic fragment or variant thereof,- SEQ ID NO: 175 or an immunogenic fragment or variant thereof,- SEQ ID NO: 176 or an immunogenic fragment or variant thereof,- SEQ ID NO: 177 or an immunogenic fragment or variant thereof,- SEQ ID NO: 178 or an immunogenic fragment or variant thereof, or- SEQ ID NO: 179 or an immunogenic fragment or variant thereof.

50. The artificial nucleic acid of claim 49, wherein the at least one encoded polypeptide or protein comprises or consists of the amino acid sequence according to SEQ ID NOs: 173 or 179, or of an immunogenic fragment or variant of any of these sequences, preferably wherein the immunogenic fragment or variant comprises or consists of an amino acid sequence being at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 173 or 179.

51. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises or consists of an amino acid sequence according to- SEQ ID NO: 180 or an immunogenic fragment or variant thereof,- SEQ ID NO: 181 or an immunogenic fragment or variant thereof,- SEQ ID NO: 182 or an immunogenic fragment or variant thereof,- SEQ ID NO: 183 or an immunogenic fragment or variant thereof,- SEQ ID NO: 184 or an immunogenic fragment or variant thereof,- SEQ ID NO: 185 or an immunogenic fragment or variant thereof,- SEQ ID NO: 186 or an immunogenic fragment or variant thereof, or- SEQ ID NO: 187 or an immunogenic fragment or variant thereof.

52. The artificial nucleic acid of claim 51 , wherein the at least one encoded polypeptide or protein comprises or consists of the amino acid sequence according to SEQ ID NOs: 181 or 187, or of an immunogenic fragment or variant of any of these sequences, preferably wherein the immunogenic fragment or variant comprises or consists of an amino acid sequence being at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 181 or 187, preferably wherein the immunogenic fragment or variant comprises or consists of an amino acid sequence being at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 187.

53. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein from at least one of the TAAs BCAN, NLGNX4, PTPRZ1 , BIRC5 or ELOVL2, or from a variant thereof, comprising or consisting of- at least one MHC-I epitope, wherein the at least one MHC-I epitope is an HLA-A epitope, preferably an HLA-A*02 epitope, more preferably an HI_A-A*02:01 epitope, and / or- at least one MHC-II epitope, wherein the at least one MHC-II epitope is an HLA-DR epitope that can be presented by at least one HLA-DR allele, preferably by multiple HLA-DR alleles.

54. The artificial nucleic acid of any one of the preceding claims, wherein the artificial nucleic acid is suitable for vaccination of subjects expressing HLA-A allele HLA-A*02, preferably expressing HLA- A*02:01 .

55. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein from at least one of the TAAs BCAN, NLGNX4, PTPRZ1 , BIRC5 or ELOVL2, or from a variant thereof, comprising or consisting of at least one MHC-I epitope, wherein the at least one MHC-I epitope is an HLA-A / B / C epitope other than a HLA-A*02 or a HLA-A*02:01 epitope.

56. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein comprises at least one antigenic peptide or protein from at least one of the TAAs BCAN, NLGNX4, PTPRZ1 , BIRC5 or ELOVL2, or from a variant thereof, comprising or consisting of at least one MHC-I epitope, wherein the at least one MHC-I epitope is an HLA-A / B / C epitope, wherein HLA-A / B / C is an allele expressed by at least 5, 10, 15, 20, 25, 30, 35, 40, 50, or 60% of the human population in Europe, North America and / or Asia.

57. The artificial nucleic acid of any one of the preceding claims, wherein the artificial nucleic acid is suitable for vaccination of subjects that do not express HLA-A allele HLA-A*02 or HLA-A*02:01 .

58. The artificial nucleic acid of any one of the claims 53 to 57, wherein at least one MHC-I and / or MHC-II epitope is present or predicted to be present on tumour cells of at least 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, 96, 97, 98, 99% or 100% of subjects with- glioblastoma and / or astrocytoma,- MGMT-unmethylated glioblastoma and / or astrocytoma with a molecular signature of unmethylated glioblastoma, and / or- “unmethylated” glioblastoma of CNS WHO Grade 4 and / or isocitrate dehydrogenase (IDH)-wild type astrocytoma with a molecular signature of “unmethylated” glioblastoma, wherein the subjects are optionally newly-diagnosed and / or surgically resected.

59. The artificial nucleic acid of any one of the preceding claims, wherein the artificial nucleic acid is suitable for vaccination of at least 20, 30, 40, 50, 60, 70, 80, 90, 95, 96, 97, 98, 99% or of 100% of the subjects as defined in claim 58.

60. The artificial nucleic acid of any one of the preceding claims, wherein the artificial nucleic acid is suitable for inducing a CD8 and / or CD4 immune response in a subject as defined in claim 58, whereinthe immune response is directed against at least one of the encoded antigenic peptides or proteins from at least one of the TAAs BCAN, NLGNX4, PTPRZ1 , BIRC5 or ELOVL2, or from a variant thereof.

61. The artificial nucleic acid of any one of the preceding claims, wherein the artificial nucleic acid is suitable for inducing a CD8 and / or CD4 immune response in a subject as defined in claim 58, wherein the immune response is directed against- at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 MHC-I epitopes from the TAAs, more preferably against at least 1 , 2, 3, 4, 5, or 6 amino acid sequences or immunogenic fragments or variants as specified in claim 13 or 14, and / or- at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 MHC-II epitopes, more preferably against at least 1 , 2, or 3 amino acid sequences or immunogenic fragments or variants as specified in claim 17.

62. The artificial nucleic acid of any one of the preceding claims, wherein the artificial nucleic acid is suitable for inducing a CD8 and / or CD4 immune response in a subject, wherein the immune response is directed against the at least one antigenic peptide or protein from the viral antigen as specified in claim 20 or 21 or from a variant thereof, preferably against at least 1 , 2, or 3 MHC-I and / or MHC-II epitopes thereof, more preferably against at least the amino sequence according to SEQ ID NO: 139 (HBV-001) or an immunogenic fragment or variant thereof.

63. The artificial nucleic acid of any one of the preceding claims, wherein the at least one encoded polypeptide or protein does not comprise an antigenic peptide or protein from the TAA ELOVL2 or from a variant thereof.

64. The artificial nucleic acid of claim 63, wherein the at least one encoded polypeptide or protein comprises an additional amino acid sequence selected from an IRSTepm or from a variant thereof, preferably from CTI.A4 or from a variant thereof.

65. The artificial nucleic acid of any one of the preceding claims, wherein the at least one coding sequence encodes one polypeptide or protein comprising the at least one antigenic peptide or protein from each of the TAAs- Brevican core protein (BCAN) or a variant thereof,- Neuroligin-4, X-linked (NLGNX4) or a variant thereof,- Receptor-type tyrosine-protein phosphatase zeta (PTPRZ1) or a variant thereof, and- Baculoviral IAP repeat-containing protein 5 (BIRC5) or a variant thereof, optionally wherein the one polypeptide or protein additionally comprises at least one antigenic peptide or protein from the TAA ELOVL2 or from a variant thereof.

66. The artificial nucleic acid of any one of the preceding claims, wherein the artificial nucleic acid is a monocistronic, a bicistronic, or a multicistronic nucleic acid, preferably a monocistronic nucleic acid.

67. The artificial nucleic acid of claim 66, wherein the artificial nucleic acid is a bicistronic or a multicistronic nucleic acid, wherein the at least two coding sequences encode at least two polypeptides or proteins, wherein the at least two encoded polypeptides or proteins together comprise the antigenic peptides or proteins as defined in any one of the preceding claims.

68. The artificial nucleic acid of any one of the preceding claims, wherein the at least one coding sequence is a codon modified coding sequence, preferably wherein the codon modified coding sequence is selected from a C maximized coding sequence, a CAI maximized coding sequence, human codon usage adapted coding sequence, a G / C content modified coding sequence, and a G / C optimized coding sequence, or any combination thereof.

69. The artificial nucleic acid of any one of the preceding claims, wherein the at least one codon modified coding sequence is a G / C optimized coding sequence.

70. The artificial nucleic acid of any one of the preceding claims, wherein the nucleic acid comprises at least one untranslated region (UTR) element, preferably selected from at least one heterologous 5’- UTR element and / or at least one heterologous 3’-UTR element.

71. The artificial nucleic acid of claim 70, wherein the at least one 3’-UTR element comprises or consists of a nucleic acid sequence from a 3’-UTR of a gene selected from PSMB3, ALB7, alpha-globin, betaglobin, ANXA4, CASP1 , COX6B1 , FIG4, GNAS, NDUFA1 , RPS9, SLC7A3 or TUBB4B, or from a homolog, a fragment or a variant of any one of these genes, preferably wherein the at least one 3’-UTR element comprises or consists of a nucleic acid sequence being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 66-95, 112-123, or a fragment or a variant of any of these.

72. The artificial nucleic acid of claim 70 or 71, wherein the at least one 3’-UTR element comprises or consists of a nucleic acid sequence from a 3’-UTR of a PSMB3 gene, wherein the at least one 3’-UTR element comprises or consists of a nucleic acid sequence being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 66, 67, 112-123, or a fragment or a variant of any of these, preferably to SEQ ID NO: 67, or a fragment or a variant thereof.

73. The artificial nucleic acid of claim 70, wherein the at least one 5’-UTR element comprises or consists of a nucleic acid sequence from a 5’-UTR of a gene selected from HSD17B4, RPL32, AIG1 , alpha-globin, ASAH1 , ATP5A1 , COX6C, DPYSL2, MDR, MP68, NDUFA4, NOSIP, RPL31 , RPL35A, SLC7A3, TUBB4B, or UBQLN2, or from a homolog, a fragment or variant of any one of these genes, preferably wherein the at least one 5’-UTR element comprises or consists of a nucleic acid sequence being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 12-45, 64, 65, or a fragment or a variant of any of these.

74. The artificial nucleic acid of claim 70 or 73, wherein the at least one 5’-UTR element comprises or consists of a nucleic acid sequence from a 5’-UTR of a HSD17B4 gene, wherein the at least one 5’- UTR element comprises or consists of a nucleic acid sequence being identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of SEQ ID NOs: 12, 13, 64, 65, or a fragment or a variant of any of these, preferably to SEQ ID NO: 13, or a fragment or a variant thereof.

75. The artificial nucleic acid of any one of claims 70 to 74, wherein the at least one 5-UTR element is from HSD17B4 and the at least one 3-UTR element is from PSMB3.

76. The artificial nucleic acid of any one of the preceding claims, wherein the artificial nucleic acid is a DNA or an RNA, preferably an RNA.

77. The artificial nucleic acid of any one of the preceding claims, wherein the artificial nucleic acid is an RNA selected from an mRNA, a circular RNA, a replicon RNA, or a viral RNA.

78. The artificial nucleic acid of any one of the preceding claims, wherein the artificial nucleic acid is an mRNA.

79. The artificial nucleic acid of any one of the preceding claims, wherein the artificial nucleic acid, preferably the RNA, comprises at least one poly (A) sequence, preferably wherein the at least one poly(A) sequence comprises about 20 to about 500 adenosine nucleotides.

80. The artificial nucleic acid of claim 79, wherein the at least one poly(A) sequence comprises about 60 to about 150 adenosine nucleotides, preferably about 100 adenosine nucleotides.

81. The artificial nucleic acid of claims 79 or 80, wherein the artificial nucleic acid, preferably the RNA, comprises at least two poly(A) sequences.

82. The artificial nucleic acid of any one of claims 79 to 81 , wherein the at least one poly(A) sequence is located at the 3’ terminus, optionally, wherein the 3’-terminal nucleotide is an adenosine.

83. The artificial nucleic acid of any one of the preceding claims, wherein the artificial nucleic acid, preferably the RNA, comprises at least one poly(C) sequence and / or at least one miRNA binding site and / or at least one histone stem-loop sequence.

84. The artificial nucleic acid of any one of the preceding claims, wherein the artificial nucleic acid, preferably the RNA, comprises at least one histone stem-loop sequence, wherein said histone stemloop sequence comprises or consists of a nucleic acid sequence identical or at least 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 3 or 4, or a fragment or variant of any of these.

85. The artificial nucleic acid of any one of the preceding claims, wherein the artificial nucleic acid is an RNA that comprises at least one modified nucleotide, preferably wherein the at least one modified nucleotide is selected from pseudouridine (ip) or N1 -methylpseudouridine (ml ip), more preferably wherein the at least one modified nucleotide is N1-methylpseudouridine.

86. The artificial nucleic acid of any one of the preceding claims, wherein the artificial nucleic acid is a modified RNA, wherein each uracil is substituted by a modified nucleotide.

87. The artificial nucleic acid of any one of claims 1 to 84, wherein the artificial nucleic acid is an RNA that does not comprise a modified nucleotide.

88. The artificial nucleic acid of any one of the preceding claims, wherein the artificial nucleic acid is an RNA that comprises a 5’-cap structure.

89. The artificial nucleic acid of claim 88, wherein the 5’-cap structure is selected from a cap1 structure or a modified cap1 structure.

90. The artificial nucleic acid of any one of the preceding claims, wherein the artificial nucleic acid is an in vitro transcribed RNA.

91. The artificial nucleic acid of any one of the preceding claims, wherein the artificial nucleic acid is a purified RNA that has preferably been purified by at least one step of RP-HPLC, AEX, SEC, hydroxyapatite chromatography, TFF, filtration, precipitation, core-bead flowthrough chromatography, oligo(dT) purification, cellulose-based purification, or any combination thereof.

92. The artificial nucleic acid of any one of the preceding claims, wherein the artificial nucleic acid, preferably the RNA, is suitable for use in treatment or prevention of a disease, disorder or condition, preferably a tumour disease, disorder or condition.

93. The artificial nucleic acid of any one of the preceding claims, wherein the artificial nucleic acid, preferably the RNA, comprises the following sequence elements, preferably in 5’- to 3’-direction:- a 5’-cap structure, preferably a cap1 structure;- a 5-UTR element, preferably a 5-UTR element from a HSD17B4 gene or a fragment or variant thereof;- at least one, preferably one, coding sequence as defined in any one of the preceding claims, preferably encoding an amino acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of the amino acid sequences SEQ ID NOs: 156-163, 172-179, or 180-187, or an immunogenic fragment or variant of any of these, more preferably encoding an amino acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of the amino acid sequences SEQ ID NOs: 157, 163, 173, 179, 181, or 187, or an immunogenic fragment or variant of any of these;- a 3-UTR element, preferably a 3-UTR element from a PSMB3 gene or a fragment or variant thereof;- optionally, a histone stem-loop; and- a poly(A) sequence, preferably comprising about 100 A nucleotides.

94. The artificial nucleic acid of any one of the preceding claims, wherein the artificial nucleic acid is an mRNA that comprises the following sequence elements in 5’- to 3’-direction:- a 5’-cap structure, preferably a cap1 structure;- a 5-UTR element that comprises or consists of a nucleic acid sequence being identical or at least 80% identical to SEQ ID NO: 13, or a fragment or a variant thereof;- at least one, preferably one, coding sequence as defined in any one of the preceding claims, preferably comprising or consisting of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of the nucleic acid sequences SEQ ID NOs: 240-247, 256-263, or 264-271 , or a fragment or variant of any of these, more preferably comprising or consisting of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%,97%, 98%, or 99% identical to any one of the nucleic acid sequences SEQ ID NOs: 241, 247, 257, 263, 265, or 271 , or a fragment or variant of any of these;- a 3-UTR element that comprises or consists of a nucleic acid sequence being identical or at least 80% identical to SEQ ID NO: 67, or a fragment or a variant thereof;- optionally, a histone stem-loop, preferably comprising or consisting of a nucleic acid sequence identical or at least 80% identical to SEQ ID NO: 4, or a fragment or variant of any of these;- a poly(A) sequence, preferably comprising about 100 A nucleotides.

95. The artificial nucleic acid of any one of the preceding claims, wherein the artificial nucleic acid is an mRNA comprising or consisting of a nucleic acid sequence that is identical or at least 70%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to any one of the nucleic acid sequences SEQ ID NOs: 298, 304, 314, 320, 322, or 328, or a fragment or variant of any of these, preferably to SEQ ID NO: 328 or a fragment or variant of thereof, more preferably, wherein the mRNA has a 5’-cap structure.

96. An artificial nucleic acid set comprising at least two distinct artificial nucleic acids, wherein each of the at least two distinct artificial nucleic acids comprises at least one coding sequence encoding at least one polypeptide or protein, wherein the at least two encoded polypeptides or proteins together comprise at least one antigenic peptide or protein from each of the TAAs- BCAN or a variant thereof,- NLGNX4 or a variant thereof,- PTPRZ1 or a variant thereof, and- BIRC5 or a variant thereof.

97. The artificial nucleic acid set of claim 96, wherein the at least two encoded polypeptides or proteins together comprise the antigenic peptides or proteins that are encoded by the at least one coding sequence of the artificial nucleic acid as defined in any one of claims 1 to 95.

98. The artificial nucleic acid set of claim 96 or 97, wherein the at least two encoded polypeptides or proteins comprise at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 antigenic peptides from at least one of the TAAs BCAN, NLGNX4, PTPRZ1 , BIRC5 or ELOVL2, or from a variant thereof.

99. The artificial nucleic acid set of claim 98, wherein the at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 antigenic peptides from the same TAA or variant thereof are comprised in the same encoded polypeptide or protein of the at least two encoded polypeptides or proteins.

100. The artificial nucleic acid set of any one of claims 96 to 99, wherein at least one, preferably each, of the at least two distinct artificial nucleic acids is characterized by any of the features as defined in any one of claims 1 to 64.

101. The artificial nucleic acid set of any one of claims 96 to 100, wherein at least one, preferably each, of the at least two encoded polypeptides or protein comprises- at least one linker element as defined in claim 33,- at least one additional amino acid sequence selected from an IRSTepm or from a variant thereof as defined in claim 34 or 35,- at least one additional amino acid sequence selected from a signal peptide or from a variant thereof as defined in claim 36 or 37, and / or- at least one amino acid sequence selected from a modulator element as defined in any one of claims 38 to 46 or claims 165 to 181.

102. The artificial nucleic acid set of any one of claims 96 to 101, wherein at least one, preferably each, of the at least two distinct artificial nucleic acids is characterized by any of the features as defined in any one of claims 66 to 95.

103. A pharmaceutical composition comprising- an artificial nucleic acid as defined in any one of claims 1 to 95, or- an artificial nucleic acid set as defined in any one of claims 96 to 101.

104. The pharmaceutical composition of claim 103, wherein the at least two artificial nucleic acids of the artificial nucleic acid set are co-formulated in one entity or formulated in separate entities.

105. The pharmaceutical composition of claim 103 or 104, comprising at least one pharmaceutically acceptable carrier or pharmaceutically acceptable excipient.

106. The pharmaceutical composition of any one of claims 103 to 105, wherein the least one artificial nucleic acid or artificial nucleic acid set, preferably RNA, is formulated in at least one cationic or polycationic compound.

107. The pharmaceutical composition of claim 106, wherein the at least one cationic or polycationic compound is selected from a cationic or polycationic polymer, a cationic or polycationic polysaccharide, a cationic or polycationic lipid, a cationic or polycationic protein, a cationic or polycationic peptide, or any combinations thereof.

108. The pharmaceutical composition of any one of claims 103 to 107, wherein the artificial nucleic acid or artificial nucleic acid set, preferably RNA, is formulated in a lipid-based carrier.

109. The pharmaceutical composition of claim 108, wherein the lipid-based carrier is selected from a liposome, a lipid nanoparticle, a lipoplex, solid lipid nanoparticles, lipo-polyplexes, and / or a nanoliposome.

110. The pharmaceutical composition of claim 108 or 109, wherein the lipid-based carrier is a lipid nanoparticle.

111. The pharmaceutical composition of any one of claims 108 to 110, wherein the lipid-based carrier comprises at least one lipid selected from at least one aggregation-reducing lipid, at least one cationic lipid or ionizable lipid, at least one neutral lipid or phospholipid, at least one steroid or steroid analogue.

112. The pharmaceutical composition of any one of claims 108 to 111, wherein the lipid-based carrier have a Z-average size ranging from about 50nm to about 200nm.

113. The pharmaceutical composition of any one of claims 103 to 112, the artificial nucleic acid of any one of claims 1 to 95, the artificial nucleic acid set of any one of claims 96 to 102, wherein upon administration to a cell, tissue, or subject, the encoded at least one polypeptide or protein or at least two polypeptide or protein is expressed.

114. The pharmaceutical composition of any one of claims 103 to 113, the artificial nucleic acid of any one of claims 1 to 95, the artificial nucleic acid set of any one of claims 96 to 102, wherein the pharmaceutical composition or the artificial nucleic acid or the artificial nucleic acid set is suitable for inducing a CD8 and / or CD4 immune response in a subject as defined in claim 58 against at least one of the encoded antigenic peptides or proteins from at least one of the TAAs BCAN, NLGNX4, PTPRZ1 , BIRC5 or ELOVL2, or from a variant thereof.

115. The pharmaceutical composition or the artificial nucleic acid or the artificial nucleic acid set of claim 114, wherein the pharmaceutical composition or the artificial nucleic acid or the artificial nucleic acid set is suitable for inducing a CD8 and / or CD4 immune response in a subject against- at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 MHC-I epitopes from the TAAs, more preferably against at least 1 , 2, 3, 4, 5, or 6 amino acid sequences or immunogenic fragments or variants as specified in claim 13 or 14, and / or- at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 MHC-II epitopes, more preferably against at least 1 , 2, or 3 amino acid sequences or immunogenic fragments or variants as specified in claim 17.

116. A combination of at least two pharmaceutical compositions, wherein the at least two pharmaceutical compositions together comprise at least two distinct artificial nucleic acids, wherein each of the at least two distinct artificial nucleic acids comprises at least one coding sequence encoding at least one polypeptide or protein, wherein the at least two encoded polypeptides or proteins together comprise at least one antigenic peptide or protein from each of the TAAs- BCAN or a variant thereof,- NLGNX4 or a variant thereof,- PTPRZ1 or a variant thereof, and- BIRC5 or a variant thereof.

117. The combination of claim 116, wherein each of the at least two pharmaceutical compositions comprises at least one distinct artificial nucleic acid as defined with respect to the at least two distinct artificial nucleic acids of a nucleic acid set in any one of claims 96 to 102.

118. The combination of claim 116 or 117, wherein at least one, preferably each, of the pharmaceutical compositions is characterized by any of the features defined with respect to the pharmaceutical composition of any one of claims 103 to 115.

119. The combination of 118, wherein the at least two pharmaceutical compositions are administered in a spatially separated and / or timely staggered manner.

120. A kit or kit of parts comprising an artificial nucleic acid of any one of claims 1 to 95, and / or an artificial nucleic acid set of any one of claims 96 to 102, and / or a pharmaceutical composition of any one ofclaims 103 to 115, and / or at least two pharmaceutical compositions of the combination of any one of claims of 116 to 119, optionally comprising a liquid vehicle for solubilising, and optionally comprising technical instructions providing information on administration and dosage of the components.

121. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for use as a medicament.

122. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for use as a medicament in treating or preventing cancer in a subject, or any disease, disorder, or condition related to cancer.

123. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for use as a medicament in treating or preventing glioblastoma or astrocytoma in a subject, or any disease, disorder, or condition related to glioblastoma or astrocytoma.

124. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for use as a medicament in treating or preventing i) MGMT-unmethylated glioblastoma or ii) astrocytoma with a molecular signature of unmethylated glioblastoma in a subject.

125. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for use as a medicament in treating or preventing i) “unmethylated” glioblastoma of CNS WHO Grade 4 or ii) isocitrate dehydrogenase (IDH)- wild type astrocytoma with a molecular signature of “unmethylated” glioblastoma in a subject.

126. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for the uses of any one of claims 121 to 125, wherein the artificial nucleic acid of any one of claims 1 to 95, the artificial nucleic acid set of any one of claims 96 to 102, the pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or the kit or kit of parts of claim 120 are administered to the subject by intramuscular, intradermal, intratumoral, or intravenous administration, preferably by intramuscular administration.

127. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, or a kit or kit of parts of claim 120 for the uses of any one of claims 121 to 125, wherein a pharmaceutical composition comprising the artificial nucleic acid of claim 95 is administered to the subject.

128. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for the uses of any one of claims 121 to 127, wherein the subject is a human, preferably an adult human subject.

129. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for the uses of any one of claims 121 to 128, wherein the subject is newly-diagnosed.

130. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for the uses of any one of claims 121 to 122, wherein the subject has previously undergone surgery, radiotherapy and / or chemotherapy, preferably surgery and radiotherapy and, optionally, a chemotherapy.

131. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for the uses of any one of claims 121 to 130, wherein the subject expresses at least one HLA-A*02 allele, preferably expresses HLA-A*02:01 .

132. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for the uses of any one of claims 121 to 131 , wherein the subject’s HI_A subtype and / or antigen expression and / or tumour epitope presentation is assessed prior to treatment or prevention.

133. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for the uses of any one of claims 121 to 132, wherein the at least one encoded polypeptide or protein of the artificial nucleic acid of any one of claims 1 to 95, the artificial nucleic acid set of any one of claims 96 to 102, the pharmaceutical composition of any one of claims 102 to 115, the combination of any one of claims of 116 to 119, or the kit or kit of parts of claim 120, comprises at least one antigenic peptide or protein from at least one of the TAAs BCAN, NLGNX4, PTPRZ1 , BIRC5 or ELOVL2, or from a variant thereof, comprising or consisting of at least one MHC-I epitope, wherein the at least one MHC-I epitope is an HI.A-A / B / C epitope other than a HLA-A*02 or a HI_A-A*02:01 epitope.

134. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for the uses of any one of claims 121 to 133, wherein the at least one encoded polypeptide or protein of the artificial nucleic acid of any one of claims 1 to 95, the artificial nucleic acid set of any one of claims 96 to 102, the pharmaceutical composition of any one of claims 102 to 115, the combination of any one of claims of 116 to 119, or the kit or kit ofparts of claim 120, comprises at least one antigenic peptide or protein from at least one of the TAAs BCAN, NLGNX4, PTPRZ1 , BIRC5 or ELOVL2, or from a variant thereof, comprising or consisting of at least one additional MHC-I epitope, wherein the at least one MHC-I epitope is an HI.A-A / B / C epitope, wherein HI.A-A / B / C is an allele expressed by at least 5, 10, 15, 20, 25, 30, 35, 40, 50, or 60% of the human population in Europe, North America and / or Asia.

135. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for the uses of any one of claims 121 to 134, wherein the artificial nucleic acid of any one of claims 1 to 95, the artificial nucleic acid set of any one of claims 96 to 102, the pharmaceutical composition of any one of claims 102 to 115, the combination of any one of claims of 116 to 119, or the kit or kit of parts of claim 120 is suitable for vaccination of subjects that do not express HLA-A allele HI_A-A*02 or HI_A-A*02:01 .

136. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for the uses of any one of claims 121 to 135, wherein the at least one MHC-I and / or MHC-II epitope of the artificial nucleic acid of any one of claims1 to 95, the artificial nucleic acid set of any one of claims 96 to 102, the pharmaceutical composition of any one of claims 102 to 115, the combination of any one of claims of 116 to 119, or the kit or kit of parts of claim 120 is present or predicted to be present on tumour cells of at least 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, 96, 97, 98, 99% or 100% of subjects with- glioblastoma and / or astrocytoma,- MGMT-unmethylated glioblastoma and / or astrocytoma with a molecular signature of unmethylated glioblastoma, and / or- “unmethylated” glioblastoma of CNS WHO Grade 4 and / or isocitrate dehydrogenase (IDH)-wild type astrocytoma with a molecular signature of “unmethylated” glioblastoma.

137. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for the uses of any one of claims 121 to 136, wherein the artificial nucleic acid of any one of claims 1 to 95, the artificial nucleic acid set of any one of claims 96 to 102, the pharmaceutical composition of any one of claims 102 to 115, the combination of any one of claims of 116 to 119, or the kit or kit of parts of claim 120 is for vaccination of at least 20, 30, 40, 50, 60, 70, 80, 90, 95, 96, 97, 98, 99% or of 100% of the subjects as defined in claim 136.

138. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for the uses of any one of claims 121 to 137, wherein the subject’s HI_A subtype and / or antigen expression and / or tumour epitope presentation does not have to be assessed prior to treatment or prevention.

139. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for the uses of any one of claims 121 to 138, wherein the treatment or prevention regime comprises a main period, preferably approximately 10 weeks of vaccination, and an optional maintenance period, preferably approximately 36 weeks of vaccination.

140. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for the uses of any one of claims 121 to 139, wherein the treatment or prevention regime comprises vaccinations at approximately days 1 , 8, 15, 29, 43, 57, and / or 71 in the main period, and optionally comprises vaccinations at approximately days 113, 155, 197, 239, 281 and / or 323 in the maintenance period.

141. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for the uses of any one of claims 121 to 140, wherein the treatment or prevention regime comprises a vaccination dose per day of 12-1 OOOpg mRNA, more preferably 12-100pg, most preferably approximately 12, 25, 50 or 100pg mRNA.

142. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for the uses of any one of claims 121 to 141 , wherein the treatment or prevention regime comprises a combination with at least one modality selected from radiotherapy, chemotherapy, checkpoint inhibitors, small molecule inhibitors, therapeutic antibodies or adoptive T-cell therapy.

143. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, at least two pharmaceutical compositions of the combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for the use of claim 142, wherein the vaccination is combined with temozolomide and / or a PD1 checkpoint inhibitor.

144. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for the uses of any one of claims 142 or 143, wherein the combination of the vaccination and the at least one modality is concurrently and / or sequentially.

145. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for the uses of any one of claims 121 to 144, wherein the artificial nucleic acid of any one of claims 1 to 95, the artificial nucleic acid set of any one of claims 96 to 102, the pharmaceutical composition of any one of claims 102 to 115, the combinationof any one of claims of 116 to 119, or the kit or kit of parts of claim 120 induces a CD8 and / or CD4 immune response in a subject as defined in claim 136, wherein the immune response is directed against at least one of the encoded antigenic peptides or proteins from at least one of the TAAs BCAN, NLGNX4, PTPRZ1 , BIRC5 or ELOVL2, or from a variant thereof.

146. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for the uses of any one of claims 121 to 145, wherein the artificial nucleic acid of any one of claims 1 to 95, the artificial nucleic acid set of any one of claims 96 to 102, the pharmaceutical composition of any one of claims 102 to 115, the combination of any one of claims of 116 to 119, or the kit or kit of parts of claim 120 induces a CD8 and / or CD4 immune response in a subject as defined in claim 136 against- at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 MHC-I epitopes from the TAAs, more preferably against at least 1 , 2, 3, 4, 5, or 6 amino acid sequences or immunogenic fragments or variants as specified in claim 13 or 14, and / or- at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 MHC-II epitopes, more preferably against at least 1 , 2, or 3 amino acid sequences or immunogenic fragments or variants as specified in claim 17.

147. An artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of 116 to 119, or a kit or kit of parts of claim 120 for the uses of any one of claims 121 to 146, wherein the treatment or prevention inhibits tumour growth and / or results in tumour shrinkage and / or results in the elimination of the tumour and / or prevents tumour recurrence.

148. A method of treating or preventing a disease, disorder or condition, wherein the method comprises applying or administering to a subject in need thereof an effective amount of an artificial nucleic acid of any one of claims 1 to 95, an artificial nucleic acid set of any one of claims 96 to 102, a pharmaceutical composition of any one of claims 103 to 115, a combination of any one of claims of116 to 119, or a kit or kit of parts of claim 120.

149. The method oftreating or preventing a disease, disorder or condition of claim 148, wherein the method is characterized by any of the features as specified in any one of claims 119 to 147.

150. An artificial nucleic acid comprising at least one coding sequence, wherein the at least one coding sequence encodes at least one encoded polypeptide or protein, the at least one polypeptide or protein comprising at least one antigenic peptide or protein and at least one amino acid sequence from a modulator element, wherein the modulator element modulates / impacts the expression / translation of and / or production of and / or folding of and / or stability of and / or degradation of and / or the intracellular protein amount of and / or turnover of and / or processing for presentation by MHC molecules of and / or epitope presentation on MHC molecules of the at least one encoded polypeptide or protein, preferably wherein the modulator element is a heterologous element.

151. The artificial nucleic acid of claim 150, wherein the modulator element is a degron.

152. The artificial nucleic acid of any claim 150 or 151, wherein the modulator element is a ubiquitindependent degron.

153. The artificial nuclei acid of any one of claims 150 to 152, wherein the modulator element, preferably a degron, comprises at least one recognition site for an E3 ubiquitin ligase, preferably for a Cullin-RING E3 type ubiquitin ligase, most preferably for a CuM00^12Cullin-RING type E3 ubiquitin ligase.

154. The artificial nucleic acid of any one of claims 150 to 153, wherein the modulator element, preferably a degron, is located at the N-terminus of, at the C-terminus of, or within the amino acid sequence of the at least one encoded polypeptide or protein.

155. The artificial nucleic acid of any one of claims 150 to 154, wherein the degron comprises or consists of an amino acid sequence- of at least 2, 3, 4, or 5, preferably of 5 glutamic acids and is preferably located at the C-terminus of the at least one encoded polypeptide or protein,- of at least 2, 3, 4, or 5, preferably of 5 glycines, and is preferably located at the C-terminus of the at least one encoded polypeptide or protein,- of at least 2, 3, 4, or 5, preferably of 5 arginines, and is preferably located at the N- or C- terminus of the at least one encoded polypeptide or protein, or- of at least 2, 3, 4, or 5, preferably of 5 lysines, and is preferably located at the N-terminus of the at least one encoded polypeptide or protein.

156. The artificial nucleic acid of any one of claims 150 to 155, wherein the at least one encoded polypeptide or protein comprising the modulator element, preferably a degron, is characterized by- a decreased folding of, and / or- a decreased stability of, and / or- an increased degradation of, and / or- a decreased intracellular protein amount of, and / or- an increased turnover of, and / or- an increased processing for presentation by MHC-I and / or MHC-II molecules of, and / or- an increased retention time in endosomal-lysosomal vesicles of, and / or- an increased loading of MHC-I and / or MHC-II molecules, and / or- an increased epitope presentation on MHC-I and / or MHC-II molecules upon artificial nucleic acid administration compared to a corresponding polypeptide or protein without the modulator element.

157. The artificial nucleic acid of any one of the claims 150 to 156, wherein the at least one encoded polypeptide or protein comprising the modulator element, preferably a degron, more preferably a degron as defined in any one of claims 150 to 156, more preferably a degron comprising or consisting of an amino acid sequence of at least 2, 3, 4, or 5 glutamic acids, additionally comprises at least one additional amino acid sequence selected from an IRSTepm or from a variant thereof.

158. The artificial nucleic acid of claim 157, wherein the at least one additional amino acid sequence selected from an IRSTepm or from a variant thereof is an amino acid sequence from CTLA4 or from avariant thereof, preferably the amino acid sequence according to SEQ ID NO: 201 or a fragment or variant thereof.

159. The artificial nucleic acid of claim 157 or 158, wherein the at least one additional amino acid sequence is located C-terminally of the most C-terminal antigenic peptide or protein, or of a linker element fused C-terminally to said antigenic peptide or protein.

160. The artificial nucleic acid of any one of claims 157 to 159, wherein the modulator element, preferably a degron, more preferably a degron as defined in any one of claims 150 to 156, most preferably a degron comprising or consisting of an amino acid sequence of at least 2, 3, 4, or 5 glutamic acids, is located C-terminally of an additional amino acid sequence selected from an IRSTepm, preferably located C-terminally of an additional amino acid sequence from an IRSTepm as defined in any one of claims 157 to 159.

161. The artificial nucleic acid of any one of claims 150 to 155 and 157 to 160, wherein the at least one encoded polypeptide or protein comprising the modulator element, preferably a degron, is characterized by- an increased expression / translation of, and / or- an increased production of, and / or- an increased folding of, and / or- an increased stability of, and / or- a decreased degradation of, and / or- an increased intracellular protein amount of, and / or- a decreased turnover of, and / or- an increased processing for presentation by MHC-I and / or MHC-II molecules of, and / or- an increased retention time in endosomal-lysosomal vesicles of, and / or- an increased loading of MHC-I and / or MHC-II molecules, and / or- an increased epitope presentation on MHC-I and / or MHC-II molecules upon artificial nucleic acid administration compared to a corresponding polypeptide or protein without the modulator element.

162. The artificial nucleic acid of any one of claims 150 to 155 and 157 to 161 , wherein the at least one encoded polypeptide or protein comprising the modulator element, preferably a degron, is characterized by an increased intracellular protein amount upon artificial nucleic acid administration compared to a corresponding polypeptide or protein without the modulator element.

163. The artificial nucleic acid of any one of claims 150 to 155 and 157 to 162, wherein the at least one encoded polypeptide or protein comprising the modulator element, preferably a degron, is characterized by an increased presentation of at least one MHC-II epitope comprised in the at least one encoded polypeptide or protein upon artificial nucleic acid administration compared to a corresponding polypeptide or protein without the modulator element.

164. The artificial nucleic acid of any one of claims 150 to 163, wherein the nucleic acid is characterized by any one of the general nucleic acid features of any one of claims 66 to 92.

165. A composition of the artificial nucleic acid of any one of claims 150 to 164, wherein the composition is characterized by any one of the features as defined with respect to the pharmaceutical composition of any one of claims 105 to 115.

166. A polypeptide or protein comprising a modulator element, wherein the modulator element and the polypeptide or protein are characterized by any one of the features as defined in any one of claims 150 to 164, preferably wherein the modulator element comprises an amino acid sequence as defined in claim 155.

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