Adenoviral targeting of dendritic cells

Abstract

Disclosed herein are adapters containing designed ankyrin repeat protein domains fused to peptides, scFv or viral glycoproteins specifically designed to target antigen presenting cells (APCs), such as dendritic cells (DCs). Adenoviruses armed with such adapters efficiently transduce human dendritic cells and can be utilized for therapeutic approaches, such as tumor vaccination or direct delivery of payloads (such as stimulatory cytokines) into lymph nodes.

Description

[0001]Adenoviral targeting of dendritic cells Background The clinical utility of B- and T-cell vaccines is undisputed, and adenoviral vectors have shown encouraging results. Nonetheless, HAdV5, the most widely used and studied serotype, transduces dendritic cells and macrophages only poorly and only at very high viral loads (see for example Science (2018) 359: 1355-60; Nature Cancer (2022) 3:911-26). The present invention provides a system by which adenoviruses can be efficiently transduced into dendritic cells. The system can be efficiently used to boost vaccination, for example by using HC-HAdV5 for combination with T cell stimulatory cytokines. Using HC-HAdV5 with its large encoding capacity instead of the commonly used HAdV5 opens new doors for example in the field of vaccination or dendritic cell targeted gene therapy. Summary of the invention The present invention relates to a recombinant protein comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain. In certain embodiments said polypeptide specifically binding to said antigen present on dendritic cell is a polypeptide specific for an antigen selected from CD11c, DEC-205 and DC-SIGN. In certain embodiments said polypeptide specifically binding to said antigen present on dendritic cell is a polypeptide specific for CD11c. In certain embodiments said polypeptide specific for CD11c is selected from a polypeptide comprising an amino acid sequence of SEQ ID No.18, 19, 20, 21, 22, 23 or 57. In certain embodiments said polypeptide specifically binding to said antigen present on dendritic cell is a polypeptide specific for DEC-205. In certain embodiments said polypeptide specific for DEC- 205 is selected from a polypeptide comprising an amino acid sequence of SEQ ID No.24, 25, 26, 27, 28, 29 or 30. In certain embodiments said polypeptide specifically binding to said antigen present on dendritic cell is a polypeptide specific for DC-SIGN. In certain embodiments said polypeptide specific for DC-SIGN is selected from a polypeptide comprising an amino acid sequence of SEQ ID No.36, 37, or 38. In certain embodiments, said recombinant protein comprising from the N- to the C-terminus a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain. In certain embodiments said designed ankyrin repeat domain that specifically binds to the knob of an adenovirus comprises the amino acid sequence of SEQ ID No.2. In certain embodiments, said trimerization domain is or is derived from the capsid protein SHP of lambdoid phage 21. In certain embodiments, said trimerization domain comprises the amino acid sequence of SEQ ID No.1. In certain embodiments, said recombinant protein comprising from the N- to the C-terminus a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain, comprises a amino acid sequence selected from SEQ ID Nos.26-40 or 56. In certain embodiments, the present invention relates to a nucleic acid encoding any of aforementioned recombinant proteins. In certain embodiments, the present invention relates to a trimeric protein comprising three of aforementioned recombinant proteins. In certain embodiments, the present invention relates to recombinant adenovirus displaying any of aforementioned recombinant proteins or trimeric proteins. In certain embodiments, said adenovirus is of adenovirus serotype 5 or wherein said adenovirus comprises a knob of an adenovirus of serotype 5. In certain embodiments, the present invention relates to any of aformentioned recombinant adenoviruses, the recombinant proteins or the trimeric proteins for use in the transduction of dendritic cells or macrophages. In certain embodiments, the present invention relates to any of aformentioned recombinant adenoviruses, the recombinant proteins or the trimeric proteins for use in medicine. Figure legends Figure 1 shows the adapter screening and increased transduction of the murine dendritic cell line DC2.4 with a HAdV5HVR7coding for tdTomato at a MOI (infectious particles) 100 or 25 of mono-or dual- adapters. Mono-adapters: 1-25 (retargeting domains SEQ. ID No 14-38) and dual adapters: 26-40 (Table 2). B= knob blocking, V= untargeted virus, C= cells (neg. control). Figure 2 depicts GP of Lassa mammarenavirus (LASV) including selected domains and glycosylation sites. Figure 3 shows that DARPin adapters carrying GP, or variants of GP, of LASV strongly increase the transduction efficiency on the murine dendritic cell line DC2.4. The effect is particular pronounced for targeting domains that carry the M192R mutation (GP1-adapter). GP1-adapter (retargeting domain SEQ ID No 36), GP1 / GP2-adapter (retargeting domain SEQ ID No 37), GP1 wt-adapter (retargeting domain SEQ ID No 38). P-value determined using one-way ANOVA with Dunnett’s test for multiple comparisons to untargeted control. Bar graphs represent mean ± SD, n = 4. Figure 4 shows that a DARPin adapter ( ^-DC adapter) carrying the GP1 targeting domain of LASV GP with a M192R mutation together with the loop 4 of ICAM1, targeting the CD11c moiety leads to a strong induction of the transduction efficiency in dendritic cell lines at various MOI (100 or 25). DC2.4 transduced by HAdV5HVRencoding for tdTomato (A) or ffLuciferase (B). MutuDC transduced by HAdV5HVRencoding for ffLuciferase (C). In comparison, adapters carrying the GP1 targeting domain of LASV GP with a M192R mutation but without the loop 4 of ICAM1 (GP1-adapter) lead to less high transduction rates. HAdV5 only pre-incubated with 1 µM human lactoferrin lead to less high transduction rates. Transduction of targeted (+ ^-DC adapter) HAdV5 can be blocked by antibodies binding to DC-SIGN or CD11c, confirming the specific cell entry by those receptors. P-value determined using one-way ANOVA with Dunnett’s test for multiple comparisons to untargeted control. Bar graphs represent mean ± SD, n = 4. Figure 5 shows that a DARPin adapter (a-DC adaper) carrying the GP1 targeting domain of LASV GP with a M192R mutation together with the loop 4 of ICAM1, targeting CD11c, leads to a strong induction of the transduction of murine primary dendritic cells (BMDC). In comparison, adapters carrying the GP1 targeting domain of LASV GP with a M192R mutation but without the loop 4 of ICAM1 (GP1- adapter) leads to less high transduction rates. HAdV5 only pre-incubated with 1 µM human lactoferrin also lead to less high transduction rates. Transduction of targeted (+ ^-DC adapter) HAdV5 can be blocked by antibodies binding to DC-SIGN or CD11c, confirming the specific cell entry by those receptors. P-value determined using one-way ANOVA with Dunnett’s test for multiple comparisons to untargeted control. Bar graphs represent mean ± SD, n = 4. Figures 6 and 7 shows that a DARPin adapter ( ^ ^DC adapter) carrying the GP1 targeting domain of LASV GP with a M192R mutation together with the loop 4 of ICAM1, targeting CD11c, leads to a strong induction of the transduction of human primary dendritic cells also at a low MOI. Primary hDC from Donor1 transduced by HAdV5HVRencoding for ffLuciferase (6A) at MOI 100 or 25. In comparison, adapters carrying the GP1 targeting domain of LASV GP with a M192R mutation but without the loop 4 of ICAM1 (GP1-adapter) lead to less high transduction rates. HAdV5 only pre-incubated with 1 µM human lactoferrin lead to less high transduction rates. Primary hDC from Donor1 transduced by HAdV5HVRencoding for ffLuciferase (6B) express the transgene over a long timecourse for at least 10 days. The retargeting effect to primary hDCs can also be replicated with alternative donors, Donor2 (7A) or Donor3 (7B), confirming the beneficial effect of the ^-DC adapter at MOI 25, 12.5 or 6.25. In summary, the increase of measured reporter protein activity (Luciferase) is multiplied by factor 5-20 (dependent on MOI, donor and timepoint). P-value determined using one-way ANOVA with Dunnett’s test for multiple comparisons to untargeted control. Bar graphs represent mean ± SD, n = 4. Figure 8 shows that the dual-module DARPin adapter targeted HAdV5HVR7leads to a significant increase of luciferase expression in lymph nodes (A), but not in the liver (B) or the spleen (C). P-value determined using two-tailed paired t tests. Bar graphs represent mean ± SD, n = 5. Figure 9 shows that mice injected with B16-OVA MO4 cells and two times vaccinated with HAdV5 or HC-HAdV5 (antigen li-OVA.1+2) - with the dual targeting DARPin adapters - show a significant rise of cytotoxic T cells (CD3+ cells binding to MHCI dextramer with peptide SIINFEKL) (A), (C) or responsive splenocytes (B) In case of co-expressing cytokine (mu IL2v or mu IL21) this increase shown is most prominent. The study was done with low load injections of 1x107vp (i.p.) (A), (B) or high load injections 3x108vp (i.p.) (C). P-value determined using two-tailed paired t tests or one-way ANOVA with Dunnett’s test for multiple comparisons to untargeted control. Bar graphs represent mean ± SD, n = 5- 7. Figure 10 shows that mice injected with B16-OVA MO4 cells and two times vaccinated with HAdV5 or HC-HAdV5 (antigen li-OVA.1+2) develop an immunoglobulin response. The study was done with low load injections of 1x107vp (i.p.) (A), (B) or high load injections 3x108vp (i.p.) (C), (D). In case of retargeting adapters with co-expression of mu IL2v or mu IL21, a significant increase of a factor 3 of IgG levels against the encoded antigen was detected in the mouse serum (C) ( ^-Ovalbumin IgGs). In contrast, IgG levels against the adenoviral protein (hexon) do not increase in case of adapter nor cytokine co-expression (B), (D). P-value determined using two-tailed paired t tests or one-way ANOVA with Dunnett’s test for multiple comparisons to untargeted control. Bar graphs represent mean ± SD, n = 5-7. Figure 11 shows that mice injected with B16-OVA MO4 cells and two times vaccinated with HAdV5 or HC-HAdV5 (antigen li-OVA.1+2) - with the dual targeting DARPin adapters - show a pronounced tumor regression as measured by the weight of the lung (A), (D), the number of metastatic foci on the lung surface (B), (E), and the melanin content in lung cell lysate (C), (F). The most significant effect was seen for the retargeted treatment groups with co-expression of mu IL2v or mu IL21. The study was done with low load injections of 1x107vp (i.p.) (A), (B), (C) or high load injections 3x108vp (i.p.) (D), (E), (F). P-value determined using two-tailed paired t tests or one-way ANOVA with Dunnett’s test for multiple comparisons to untargeted control. Bar graphs represent mean ± SD, n = 5-7. Definitions The term “recombinant” as used in recombinant protein, recombinant protein domain and the like, means that said polypeptides are produced by the use of recombinant DNA technologies well known by the practitioner skilled in the relevant art. For example, a recombinant DNA molecule (e.g. produced by gene synthesis) encoding a polypeptide can be cloned into a bacterial expression plasmid (e.g. pQE30, Qiagen). When such a constructed recombinant expression plasmid is inserted into a host cell (e.g. E. coli), this host cell can produce the polypeptide encoded by this recombinant DNA. The correspondingly produced polypeptide is called a recombinant polypeptide. The term “protein” as used herein refers to a polypeptide, wherein at least part of the polypeptide has, or is able to, acquire a defined three-dimensional arrangement by forming secondary, tertiary, or quaternary structures within and / or between its polypeptide chain(s). If a protein comprises two or more polypeptides, the individual polypeptide chains may be linked non-covalently or covalently, e.g. by a disulfide bond between two polypeptides. A part of a protein, which individually has, or is able to acquire a defined three-dimensional arrangement by forming secondary or tertiary structures, is termed "protein domain" or “domain”. Such protein domains are well known to the practitioner skilled in the art. The term "polypeptide" as used herein refers to a molecule consisting of one or more chains of multiple, i.e. two or more, amino acids linked via peptide bonds. A polypeptide typically consists of more than twenty amino acids linked via peptide bonds. The term “peptide” as used herein refers to a molecule consisting of one or more chains of multiple, i.e. two or more, amino acids linked via peptide bonds. A peptide typically consists of not more than twenty amino acids linked via peptide bonds. The terms “designed ankyrin repeat protein”, “designed ankyrin repeat domain” and “DARPin” as used herein refer to artificial polypeptides, comprising several ankyrin repeat motifs. These adjacent ankyrin repeat motifs provide a rigid interface arising from typically several adjacent helices and β- turns. DARPins usually carry two or three repeats corresponding to an artificial consensus sequence, wherein six positions per repeat are randomized, flanked by two capping repeats with a hydrophilic surface (Curr Opin Chem Biol (2009) 13:245-55; WO 02 / 20565). The term “antibody” as used herein refers to a protein comprising at least two heavy (H) chains and two light (L) chains inter-connected by disulfide bonds, which interacts with an antigen. Each heavy chain is comprised of a heavy chain variable region (abbreviated herein as VH) and a heavy chain constant region. The heavy chain constant region is comprised of three domains, CH1, CH2 and CH3. Each light chain is comprised of a light chain variable region (abbreviated herein as VL) and a light chain constant region. The light chain constant region is comprised of one domain, CL. The VH and VL regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDR), interspersed with regions that are more conserved, termed framework regions (FR). Each VH and VL is composed of three CDRs and four FR’s arranged from amino-terminus to carboxy- terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. The variable regions of the heavy and light chains contain a binding domain that interacts with an antigen. The constant regions of the antibodies may mediate the binding of the immunoglobulin to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (C1q) of the classical complement system. The term “antibody” includes for example, monoclonal antibodies, human antibodies, humanized antibodies, camelised antibodies and chimeric antibodies. The antibodies can be of any isotype (e.g., IgG, IgE, IgM, IgD, IgA and IgY), class (e.g., IgG1, lgG2, lgG3, lgG4, lgA1 and lgA2) or subclass. Both the light and heavy chains are divided into regions of structural and functional homology. The term “antibody fragment” as used herein refers to one or more portions of an antibody that retain the ability to specifically interact with (e.g., by binding, steric hindrance, stabilizing spatial distribution) an antigen. Examples of binding fragments include, but are not limited to, a Fab fragment, a monovalent fragment consisting of the VL, VH, CL and CH1 domains; a F(ab)2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; a Fd fragment consisting of the VH and CH1 domains; a Fv fragment consisting of the VL and VH domains of a single arm of an antibody; a dAb fragment (Ward et al., (1989) Nature 341 :544-546), which consists of a VH domain; and an isolated complementarity determining region (CDR). Furthermore, although the two domains of the Fv fragment, VL and VH, are coded for by separate genes, they can be joined, using recombinant methods, by a synthetic linker that enables them to be made as a single protein chain in which the VL and VH regions pair to form monovalent molecules (known as “single chain variable fragment”, “single chain Fv” or “scFv”; see e.g., Bird et al., (1988) Science 242:423-426; and Huston et al., (1988) Proc. Natl. Acad. Sci.85:5879-5883). Such single chain antibodies are also intended to be encompassed within the term “antibody fragment”. These antibody fragments are obtained using conventional techniques known to those of skill in the art, and the fragments are screened for utility in the same manner as are intact antibodies. Antibody fragments can also be incorporated into single domain antibodies, maxibodies, minibodies, intrabodies, diabodies, triabodies, tetrabodies, v-NAR and bis-scFv (see, e.g., Hollinger and Hudson, (2005) Nature Biotechnology 23:1126-1136). Antibody fragments can be grafted into scaffolds based on polypeptides such as Fibronectin type III (Fn3) (see U.S. Pat. No.6,703,199, which describes fibronectin polypeptide monobodies). Antibody fragments can be incorporated into single chain molecules comprising a pair of tandem Fv segments (VH-CH1 - VH-CH1) which, together with complementary light chain polypeptides, form a pair of antigen-binding sites (Zapata et al., (1995) Protein Eng.8: 1057-1062; and U.S. Pat. No.5,641 ,870). The term “immunoglobulin” as used herein refers to any polypeptide or fragment thereof from the class of polypeptides known to the skilled person under this designation and comprising at least one antigen binding site. Preferably, the immunoglobulin is a soluble immunoglobulin from any of the classes IgA, IgD, IgE, IgG, or IgM, or a fragment comprising at least one antigen binding site derived thereof. Also comprised as immunoglobulins of the present invention are a bispecific immunoglobulin, a synthetic immunoglobulin, an immunoglobulin fragment, such as Fab, Fv or scFv fragments etc., a single chain immunoglobulin, and a nanobody. Further included are chemically modified derivatives of any of the aforesaid, e.g. PEGylated derivatives, as well as fusion proteins comprising any of the aforesaid immunoglobulins and fragments thereof. The immunoglobulin may be a human or humanized immunoglobulin, a primatized, or a chimerized immunoglobulin or a fragment thereof as specified above. Preferably, the immunoglobulin of the present invention is a polyclonal or a monoclonal immunoglobulin, more preferably a monoclonal immunoglobulin or a fragment thereof as specified above. The terms “binds”, “is specific” and “specifically binds” as used herein refers to a molecule, for example an antibody or an antibody fragment, which recognizes a specific antigen, but does not substantially recognize or bind other molecules in a sample. An antibody that specifically binds to an antigen from one species may also bind to that antigen from one or more further species. Such cross- species reactivity does not itself alter the classification of an antibody as specific. The terms “binding domain” and “antigen binding domain” as used herein are art recognized and refers to refers to a portion of a binding molecule that binds to an antigen or an epitope of an antigen. Preferably, said binding molecule is a proteinaceous molecule. Exemplary molecules containing binding domains are polypeptides, peptides, antibodies or antibody fragments, such as scFv’s. The terms "cross-reactive" and “cross reactive” as used herein refer to a property of a binding protein or binding domain, such as a DARPin, to bind to more than one antigen of a similar type or class, such as an ortholog of an antigen. For example such binding protein may bind to the human and the non-human primate ortholog of the same antigen or to the human and the rodent ortholog of the same antigen. In preferred embodiments of the present disclosure the binding protein may bind to the human and the mouse ortholog of the same antigen. The term “nucleic acid” as used herein refers to a polymeric form of nucleotides of any length, either ribonucleotides or deoxyribonucleotides. Thus, this term includes, but is not limited to, single-, double-, or multi-stranded DNA or RNA, genomic DNA, cDNA, DNA-RNA hybrids, or a polymer comprising purine and pyrimidine bases or other natural, chemically or biochemically modified, non- natural, or derivatized nucleotide bases. The term “vector” as used herein means a construct, which is capable of delivering, and usually expressing or regulating expression of, one or more gene(s) or nucleic acid(s) of interest in a host cell. Examples of vectors include, but are not limited to, viral vectors, naked DNA or RNA expression vectors, plasmid, cosmid, or phage vectors, DNA or RNA expression vectors associated with cationic condensing agents, and DNA or RNA expression vectors encapsulated in liposomes. The term “linker” as used herein refers a molecule or macromolecule serving to connect different moieties or domains of a peptide or a polypeptide or, a protein / polypeptide domain and a non- protein / non-polypeptide moiety. Linkers can be of different nature. Different domains or modules within proteins can be linked via peptide linkers. Linkers can also be generated chemically, for example to link small organic molecules or peptides to a protein. The term “flexible linker” as used herein refers to a peptide linker linking two different domains or modules of a protein and providing a certain degree of flexibility. Preferably, the flexible linker is hydrophilic and does not interacting with other surfaces. Commonly used flexible linkers are glycine- serine linkers (Biochemistry 56(50):6565-6574 (2017)). Glycine and serine are flexible and the adjacent protein domains are free to move relative to one another. Such flexible linkers are referred to herein as “glycine-serine linkers”. Other amino acids commonly used in respective linkers are proline, asparagine and threonine. Often the linker contains several repeats of a sequence of amino acids. A flexible linker used in the present disclosure is a (Gly4Ser)4-linker, i.e. a linker containing four repeats of the sequence glycine- glycine- glycine- glycine- serine. Other linkers that could be used in accordance with the present disclosure include but are not limited to PAS linkers, i.e. linkers containing repeats of the sequence proline- alanine- serine (Protein Eng Des Sel (2013) 26, 489-501 and charged linkers. The term “short linker” as used herein refers to a peptide linker linking two different domains or modules of a protein and which is no longer than four, preferably no longer than three amino acids long. More preferably the short linker is no longer than two amino acids long. Alternatively the short linker is only one amino acid long. Alternatively the short linker is a single glycine residue. The term "amino acid mutation" refers to amino acid substitutions, deletions, insertions, and modifications, as well as combinations thereof. Amino acid sequence deletions and insertions include N-and / or C-terminal deletions and insertions of amino acid residues. Particular amino acid mutations are amino acid substitutions. Amino acid substitutions include replacement by non-naturally occurring amino acids or by naturally occurring amino acid derivatives of the twenty standard amino acids. Amino acid mutations can be generated using genetic or chemical methods well known in the art. Genetic methods may include site-directed mutagenesis, PCR, gene synthesis and the like. It is contemplated that methods of altering the side chain group of an amino acid residue by methods other than genetic engineering, such as chemical modification, may also be useful. The term "variant" as used herein refers to a polypeptide that differs from a reference polypeptide by one or more amino acid mutation or modifications. The term “host cell” as used herein refers to any kind of cellular system which can be engineered to generate molecules according to the present disclosure. It should be understood that such terms are intended to refer not only to the particular subject cell but to the progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but are still included within the scope of the term “host cell” as used herein. Host cells according to the present disclosure can be a “eukaryotic host cell” and include yeast and mammalian cells, including murine cells and from other rodents, preferably vertebrate cells such as those from a mouse, rat, monkey or human cell line, for example HKB11 cells, PERC.6 cells, HEL293T cells, CHO cells or any type of HEK cells, such as HEK293 cells or HEK 993 cells. Also, suspension cell lines like CHO-S or HEK993 cells, or insect cell cultures like Sf9 cells may be used. Host cells according to the present disclosure can also be “prokaryotic cell” and include bacterial cells, such Escherichia coli. Certain strains of Escherichia coli may be particularly useful for expression of the molecules of the present disclosure, such as Escherichia coli strain DH5 (available from Bethesda Research Laboratories, Inc., Bethesda, Md / US). The molecules of the present disclosure form trimers that are highly stable. Each monomer contains a domain responsible for the formation of trimers which is referred to herein as “trimerization domain”. A preferred trimerization domain is the capsid protein SHP of lambdoid phage 21 (J Mol Biol; 344(1):179-93; PNAS 110(10):E869-77 (2013)). SHP of lambdoid phage 21 has the following amino acid sequence: VRIFAGNDPAHTATGSSGISSPTPALTPLMLDEATGKLVVWDGQKAGSAVGILVLPLEGTETALTY YKSGTFATEAIHWPESVDEHKKANAFAGSALSHAALP (SEQ ID No. 1) The term “stable trimer” or “trimeric adapter” as used herein refers to a protein trimer by protein monomers comprising a trimerization domain, and wherein said trimer exhibits a stability which is higher than other, conventional protein trimers. For example, a stable trimer has a higher functional stability, a higher kinetic stability, or a higher high life for unfolding than other protein trimers. An example of a stable trimer is a trimer formed by monomers comprising the trimerization domain of the capsid protein SHP of lambdoid phage 21. The term “derived from” in the context of an amino acid sequence refers to an amino acid sequence that is different to an original amino acid sequence, but maintains the function or activity of the original amino acid sequence. Such amino acid sequence may comprise an amino acid mutation as compared to the original amino acid sequence or may be a variant of the original amino acid sequence. The term “adenovirus” as used herein refers to any adenovirus, i.e. to human and non-human serotypes. The human isolates are classified into subgroups A-G. A preferred adenovirus of the present disclosure is adenovirus subtype 5 (“HAdV-C5”). HAdV-C5 includes modified version of the virus, such as replication-deficient HAdV-C5 version, e.g. containing an E1 / E3 deletion and / or one or more of the 4 mutations in the HVR7 (I421G, T423N, E424S and L426Y) (Nat. Commun.9, 450 (2018)). The terms “CAR” and “CXADR” as used herein refers to coxsackievirus and adenovirus receptor (UniProt: P78310). CAR is a type I membrane receptor for coxsackie viruses and adenoviruses. The term “knob” as used herein refers to a knob on the end of the adenovirus fiber (e.g. GenBank: AAP31231.1) that binds to the cellular receptor. The knob of adenovirus subtype 5 binds to CAR. Some adenoviruses carry mutations in the gene encoding the knob protein. Adenoviruses having a four– amino acid deletion within the FG loop of the knob (ΔTAYT mutation) show a decreased ability of the mutated knob to bind to CAR (Science, 286: 1568–1571 (1999); J Mol Biol 405(2):410–426). Adenoviruses carrying four amino acid mutations in the hypervariable region 7 (HVR7 mutation) show a strongly reduced binding to blood coagulation factor X (Nat Commun (2018) 9:450). The molecules of the present invention contain a designed ankyrin repeat domain that binds to the knob of an adenovirus. A preferred designed ankyrin repeat domain that binds to a knob is DARPin 1D3. Another preferred designed ankyrin repeat domain that binds to a knob is DARPin 1D3nc, a derivative of 1D3nc containing a stabilized C-cap. DARPin 1D3 has the following amino acid sequence: RSDLGKKLLEAARAGQDDEVRILMANGADANAYDHYGRTPLHMAAAVGHLEIVEVLLRNGADVNAV DTNGTTPLHLAASLGHLEIVEVLLKYGADVNAKDATGITPLYLAAYWGHLEIVEVLLKHGADVNAQ DKFGKTPFDLAIDNGNEDIAEVLQG (SEQ ID No. 2) The terms “MOI”, “moi” and “m.o.i.” as used herein refers to the multiplicity of infection as defining the ratio of infectious adenoviral particles (i.p.) to host cell. As example a MOI of 25 defines a viral load of 25 infectious adenoviral particles per seeded host cell. The term “CD40” as used herein refers to a receptor on antigen-presenting cells of the immune system and is essential for mediating a broad variety of immune and inflammatory responses including T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation. Human CD40 (UniProt: P25942) has the following amino acid sequence: MVRLPLQCVLWGCLLTAVHPEPPTACREKQYLINSQCCSLCQPGQKLVSDCTEFTETECLPCGESE FLDTWNRETHCHQHKYCDPNLGLRVQQKGTSETDTICTCEEGWHCTSEACESCVLHRSCSPGFGVK QIATGVSDTICEPCPVGFFSNVSSAFEKCHPWTSCETKDLVVQQAGTNKTDVVCGPQDRLRALVVI PIIFGILFAILLVLVFIKKVAKKPTNKAPHPKQEPQEINFPDDLPGSNTAAPVQETLHGCQPVTQE DGKESRISVQERQ (SEQ ID No. 3). The term “CD11c” (also known as ITGAX) as used herein refers to a protein which combines with the beta 2 chain (ITGB2) to form a leukocyte-specific integrin referred to as inactivated-C3b (iC3b) receptor 4 (CR4). Human CD11c (UniProt: P20702) has the following amino acid sequence: MTRTRAALLLFTALATSLGFNLDTEELTAFRVDSAGFGDSVVQYANSWVVVGAPQKITAANQTGGL YQCGYSTGACEPIGLQVPPEAVNMSLGLSLASTTSPSQLLACGPTVHHECGRNMYLTGLCFLLGPT QLTQRLPVSRQECPRQEQDIVFLIDGSGSISSRNFATMMNFVRAVISQFQRPSTQFSLMQFSNKFQ THFTFEEFRRSSNPLSLLASVHQLQGFTYTATAIQNVVHRLFHASYGARRDAAKILIVITDGKKEG DSLDYKDVIPMADAAGIIRYAIGVGLAFQNRNSWKELNDIASKPSQEHIFKVEDFDALKDIQNQLK EKIFAIEGTETTSSSSFELEMAQEGFSAVFTPDGPVLGAVGSFTWSGGAFLYPPNMSPTFINMSQE NVDMRDSYLGYSTELALWKGVQSLVLGAPRYQHTGKAVIFTQVSRQWRMKAEVTGTQIGSYFGASL CSVDVDSDGSTDLVLIGAPHYYEQTRGGQVSVCPLPRGWRRWWCDAVLYGEQGHPWGRFGAALTVL GDVNGDKLTDVVIGAPGEEENRGAVYLFHGVLGPSISPSHSQRIAGSQLSSRLQYFGQALSGGQDL TQDGLVDLAVGARGQVLLLRTRPVLWVGVSMQFIPAEIPRSAFECREQVVSEQTLVQSNICLYIDK RSKNLLGSRDLQSSVTLDLALDPGRLSPRATFQETKNRSLSRVRVLGLKAHCENFNLLLPSCVEDS VTPITLRLNFTLVGKPLLAFRNLRPMLAADAQRYFTASLPFEKNCGADHICQDNLGISFSFPGLKS LLVGSNLELNAEVMVWNDGEDSYGTTITFSHPAGLSYRYVAEGQKQGQLRSLHLTCDSAPVGSQGT WSTSCRINHLIFRGGAQITFLATFDVSPKAVLGDRLLLTANVSSENNTPRTSKTTFQLELPVKYAV YTVVSSHEQFTKYLNFSESEEKESHVAMHRYQVNNLGQRDLPVSINFWVPVELNQEAVWMDVEVSH PQNPSLRCSSEKIAPPASDFLAHIQKNPVLDCSIAGCLRFRCDVPSFSVQEELDFTLKGNLSFGWV RQILQKKVSVVSVAEITFDTSVYSQLPGQEAFMRAQTTTVLEKYKVHNPTPLIVGSSIGGLLLLAL ITAVLYKVGFFKRQYKEMMEEANGQIAPENGTQTPSPPSEK (SEQ ID No. 4). The term “CD206” (also known as MRC1) as used herein refers to a type I membrane receptor that mediates the endocytosis of glycoproteins by macrophages. Human CD206 (UniProt: P22897) has the following amino acid sequence: MRLPLLLVFASVIPGAVLLLDTRQFLIYNEDHKRCVDAVSPSAVQTAACNQDAESQKFRWVSESQI MSVAFKLCLGVPSKTDWVAITLYACDSKSEFQKWECKNDTLLGIKGEDLFFNYGNRQEKNIMLYKG SGLWSRWKIYGTTDNLCSRGYEAMYTLLGNANGATCAFPFKFENKWYADCTSAGRSDGWLWCGTTT DYDTDKLFGYCPLKFEGSESLWNKDPLTSVSYQINSKSALTWHQARKSCQQQNAELLSITEIHEQT YLTGLTSSLTSGLWIGLNSLSFNSGWQWSDRSPFRYLNWLPGSPSAEPGKSCVSLNPGKNAKWENL ECVQKLGYICKKGNTTLNSFVIPSESDVPTHCPSQWWPYAGHCYKIHRDEKKIQRDALTTCRKEGG DLTSIHTIEELDFIISQLGYEPNDELWIGLNDIKIQMYFEWSDGTPVTFTKWLRGEPSHENNRQED CVVMKGKDGYWADRGCEWPLGYICKMKSRSQGPEIVEVEKGCRKGWKKHHFYCYMIGHTLSTFAEA NQTCNNENAYLTTIEDRYEQAFLTSFVGLRPEKYFWTGLSDIQTKGTFQWTIEEEVRFTHWNSDMP GRKPGCVAMRTGIAGGLWDVLKCDEKAKFVCKHWAEGVTHPPKPTTTPEPKCPEDWGASSRTSLCF KLYAKGKHEKKTWFESRDFCRALGGDLASINNKEEQQTIWRLITASGSYHKLFWLGLTYGSPSEGF TWSDGSPVSYENWAYGEPNNYQNVEYCGELKGDPTMSWNDINCEHLNNWICQIQKGQTPKPEPTPA PQDNPPVTEDGWVIYKDYQYYFSKEKETMDNARAFCKRNFGDLVSIQSESEKKFLWKYVNRNDAQS AYFIGLLISLDKKFAWMDGSKVDYVSWATGEPNFANEDENCVTMYSNSGFWNDINCGYPNAFICQR HNSSINATTVMPTMPSVPSGCKEGWNFYSNKCFKIFGFMEEERKNWQEARKACIGFGGNLVSIQNE KEQAFLTYHMKDSTFSAWTGLNDVNSEHTFLWTDGRGVHYTNWGKGYPGGRRSSLSYEDADCVVII GGASNEAGKWMDDTCDSKRGYICQTRSDPSLTNPPATIQTDGFVKYGKSSYSLMRQKFQWHEAETY CKLHNSLIASILDPYSNAFAWLQMETSNERVWIALNSNLTDNQYTWTDKWRVRYTNWAADEPKLKS ACVYLDLDGYWKTAHCNESFYFLCKRSDEIPATEPPQLPGRCPESDHTAWIPFHGHCYYIESSYTR NWGQASLECLRMGSSLVSIESAAESSFLSYRVEPLKSKTNFWIGLFRNVEGTWLWINNSPVSFVNW NTGDPSGERNDCVALHASSGFWSNIHCSSYKGYICKRPKIIDAKPTHELLTTKADTRKMDPSKPSS NVAGVVIIVILLILTGAGLAAYFFYKKRRVHLPQEGAFENTLYFNSQSSPGTSDMKDLVGNIEQNE HSVI (SEQ ID No. 5). The term “DEC-205” (also known as LY75) as used herein refers to a protein involved in the immune response and inflammatory response. Human DEC-205 (UniProt: O60449) has the following amino acid sequence: MRTGWATPRRPAGLLMLLFWFFDLAEPSGRAANDPFTIVHGNTGKCIKPVYGWIVADDCDETEDKL WKWVSQHRLFHLHSQKCLGLDITKSVNELRMFSCDSSAMLWWKCEHHSLYGAARYRLALKDGHGTA ISNASDVWKKGGSEESLCDQPYHEIYTRDGNSYGRPCEFPFLIDGTWHHDCILDEDHSGPWCATTL NYEYDRKWGICLKPENGCEDNWEKNEQFGSCYQFNTQTALSWKEAYVSCQNQGADLLSINSAAELT YLKEKEGIAKIFWIGLNQLYSARGWEWSDHKPLNFLNWDPDRPSAPTIGGSSCARMDAESGLWQSF SCEAQLPYVCRKPLNNTVELTDVWTYSDTRCDAGWLPNNGFCYLLVNESNSWDKAHAKCKAFSSDL ISIHSLADVEVVVTKLHNEDIKEEVWIGLKNINIPTLFQWSDGTEVTLTYWDENEPNVPYNKTPNC VSYLGELGQWKVQSCEEKLKYVCKRKGEKLNDASSDKMCPPDEGWKRHGETCYKIYEDEVPFGTNC NLTITSRFEQEYLNDLMKKYDKSLRKYFWTGLRDVDSCGEYNWATVGGRRRAVTFSNWNFLEPASP GGCVAMSTGKSVGKWEVKDCRSFKALSICKKMSGPLGPEEASPKPDDPCPEGWQSFPASLSCYKVF HAERIVRKRNWEEAERFCQALGAHLSSFSHVDEIKEFLHFLTDQFSGQHWLWIGLNKRSPDLQGSW QWSDRTPVSTIIMPNEFQQDYDIRDCAAVKVFHRPWRRGWHFYDDREFIYLRPFACDTKLEWVCQI PKGRTPKTPDWYNPDRAGIHGPPLIIEGSEYWFVADLHLNYEEAVLYCASNHSFLATITSFVGLKA IKNKIANISGDGQKWWIRISEWPIDDHFTYSRYPWHRFPVTFGEECLYMSAKTWLIDLGKPTDCST KLPFICEKYNVSSLEKYSPDSAAKVQCSEQWIPFQNKCFLKIKPVSLTFSQASDTCHSYGGTLPSV LSQIEQDFITSLLPDMEATLWIGLRWTAYEKINKWTDNRELTYSNFHPLLVSGRLRIPENFFEEES RYHCALILNLQKSPFTGTWNFTSCSERHFVSLCQKYSEVKSRQTLQNASETVKYLNNLYKIIPKTL TWHSAKRECLKSNMQLVSITDPYQQAFLSVQALLHNSSLWIGLFSQDDELNFGWSDGKRLHFSRWA ETNGQLEDCVVLDTDGFWKTVDCNDNQPGAICYYSGNETEKEVKPVDSVKCPSPVLNTPWIPFQNC CYNFIITKNRHMATTQDEVHTKCQKLNPKSHILSIRDEKENNFVLEQLLYFNYMASWVMLGITYRN KSLMWFDKTPLSYTHWRAGRPTIKNEKFLAGLSTDGFWDIQTFKVIEEAVYFHQHSILACKIEMVD YKEEYNTTLPQFMPYEDGIYSVIQKKVTWYEALNMCSQSGGHLASVHNQNGQLFLEDIVKRDGFPL WVGLSSHDGSESSFEWSDGSTFDYIPWKGQTSPGNCVLLDPKGTWKHEKCNSVKDGAICYKPTKSK KLSRLTYSSRCPAAKENGSRWIQYKGHCYKSDQALHSFSEAKKLCSKHDHSATIVSIKDEDENKFV SRLMRENNNITMRVWLGLSQHSVDQSWSWLDGSEVTFVKWENKSKSGVGRCSMLIASNETWKKVEC EHGFGRVVCKVPLGPDYTAIAIIVATLSILVLMGGLIWFLFQRHRLHLAGFSSVRYAQGVNEDEIM LPSFHD (SEQ ID No. 6). The term “DC-SIGN” (also known as CD209) as used herein refers to a C-type lectin that functions in cell adhesion and pathogen recognition. Human DC-SIGN (UniProt: Q9NNX6) has the following amino acid sequence: MSDSKEPRLQQLGLLEEEQLRGLGFRQTRGYKSLAGCLGHGPLVLQLLSFTLLAGLLVQVSKVPSS ISQEQSRQDAIYQNLTQLKAAVGELSEKSKLQEIYQELTQLKAAVGELPEKSKLQEIYQELTRLKA AVGELPEKSKLQEIYQELTWLKAAVGELPEKSKMQEIYQELTRLKAAVGELPEKSKQQEIYQELTR LKAAVGELPEKSKQQEIYQELTRLKAAVGELPEKSKQQEIYQELTQLKAAVERLCHPCPWEWTFFQ GNCYFMSNSQRNWHDSITACKEVGAQLVVIKSAEEQNFLQLQSSRSNRFTWMGLSDLNQEGTWQWV DGSPLLPSFKQYWNRGEPNNVGEEDCAEFSGNGWNDDKCNLAKFWICKKSAASCSRDEEQFLSPAP ATPNPPPA (SEQ ID No. 7). The term “displaying” as used herein refers to the presentation of a polypeptide on the outside of an entity, such as an adenovirus. The polypeptides so presented on the entity may be covalently or non-covalently attached to such entity. In the context of the present disclosure, adapter molecules are recombinantly expressed and displayed on adenoviruses. This can be accomplished via a binding moiety or a scaffold, such as a designed ankyrin repeat domain that binds to the knob of an adenovirus. Alternatively, moiety or scaffold can also be genetically fused to an adenoviral protein, such as the hexon. Embodiments of the invention Disclosed herein is an adenoviral-based system for the efficient transduction of dendritic cells. The system can be used in medicine, such as diseases and disorders associated with dendritic cells or lymph nodes or for tumor vaccination. The systems allows the delivery of additional payloads to the dendritic cells, for example therapeutically active proteins, such as cytokines. Specificity of the adenoviruses is conferred by adapter molecules as described in the present disclosure. The specificity of the system and the correlating transduction efficiency is considerably higher than the systems known in the art. The system is functional with adenoviruses of any kind, including first-generation viruses, as well as high-capacity, helper virus-dependent adenoviral systems and replication-competent adenoviruses. The system is also functional with other viruses, e.g. viruses that are engineered to carry a knob of an adenovirus of subtype 5. In certain embodiments, the present disclosure relates to a recombinant adenovirus displaying a recombinant protein aa defined herein below. In certain embodiments, the present disclosure relates to a recombinant adenovirus displaying a recombinant protein aa defined herein below, wherein said recombinant protein increases the transduction of dendritic cells and wherein said recombinant protein comprises In certain embodiments, said recombinant protein increases the transduction of dendritic cells and comprises a) a binding domain specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain. In certain embodiments, said binding domain specifically binding to an antigen present on dendritic cell is a peptide specific for CD11c. In certain embodiments, said peptide specific for CD11c is selected from a peptide comprising an amino acid sequence of SEQ ID No.18, 19, 20, 21, 22, 23 or 57. In certain embodiments, said binding domain specifically binding to an antigen present on dendritic cell is a scFv specific for DEC-205. In certain embodiments, said scFv specific for DEC-205 is selected from a scFv comprising an amino acid sequence of SEQ ID No.24, 25, 26, 27, 28, 29 or 30. In certain embodiments, said binding domain specifically binding to an antigen present on dendritic cell is a polypeptide specific for DC-SIGN. In certain embodiments, said a polypeptide specific for DC- SIGN is selected from a polypeptide comprising an amino acid sequence of SEQ ID No.36, 37, or 38. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain. wherein polypeptide specifically binding to an antigen present on dendritic cell is capable of mediating the transduction of human dendritic cells. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain. wherein polypeptide specifically binding to an antigen present on dendritic cell is capable of mediating the transduction of murine and / or human dendritic cells. The system described in the present disclosure greatly enhances the transduction rate of adenoviruses for dendritic cells, in particular human dendritic cells. Adenoviruses equipped with the adapter molecules of the present disclosure have a significantly increased transduction rate as compared to wild-type adenoviruses and as compared to adenoviruses comprising other non-specific adapter molecules, while at the same time offering the possibility to deliver cargo into dendritic cells. The measurement of transduction efficiency will be a standard procedure for a person skilled in the art of flow cytometry or fluorescence microscopy, and can for example be performed as described in the Examples of the present disclosure. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain, wherein said polypeptide specifically binding to an antigen present on dendritic cell is a polypeptide specific for an antigen selected from CD11c, CD40, CD206, DEC-205 and DC-SIGN. In certain embodiments, the present disclosure relates to a recombinant protein comprising d) a polypeptide specifically binding to an antigen present on dendritic cell, e) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and f) a trimerization domain, wherein said polypeptide specifically binding to an antigen present on dendritic cell is a polypeptide specific for an antigen selected from CD11c, DEC-205 and DC-SIGN. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain, wherein said polypeptide specifically binding to an antigen present on dendritic cell is a polypeptide specific for CD11c. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain, wherein said polypeptide specifically binding to an antigen present on dendritic cell is a polypeptide specifically binding to a polypeptide of SEQ ID No.4. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to a CD11c-positive cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to CD11c on macrophages, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain, wherein said polypeptide specific for CD11c is selected from a polypeptide comprising an amino acid sequence of SEQ ID No.18, 19, 20, 21, 22, 23 or 57. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain, wherein said polypeptide specifically binding to an antigen present on dendritic cell is a polypeptide specific for DEC-205. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain, wherein said polypeptide specifically binding to an antigen present on dendritic cell is a polypeptide specifically binding to a polypeptide of SEQ ID No.6. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain, wherein said polypeptide specific for DEC-205 is selected from a polypeptide comprising an amino acid sequence of SEQ ID No.24, 25, 26, 27, 28, 29 or 30. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to a DEC-205-positive cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain, wherein said polypeptide specifically binding to an antigen present on dendritic cell is a polypeptide specific for DC-SIGN. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain, wherein said polypeptide specifically binding to an antigen present on dendritic cell is a polypeptide specifically binding to a polypeptide of SEQ ID No.7. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain, wherein said polypeptide specific for DC-SIGN is selected from a polypeptide comprising an amino acid sequence of SEQ ID No.36, 37, or 38. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to a DC-SIGN-positive cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain. In certain embodiments, the present disclosure relates to a recombinant protein comprising the amino acid sequence of any one of SEQ ID No.41-56. In certain embodiments, the present disclosure relates to a recombinant protein comprising the amino acid sequence of SEQ ID No 56. In certain embodiments, the present disclosure relates to a recombinant protein comprising the amino acid sequence of SEQ ID No 56. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a binding domain specifically binding to an antigen present on dendritic cell selected from CD11c, DEC-205 and DC-SIGN, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain. In certain embodiments, said binding domain specifically binding to an antigen present on dendritic cell is selected from a) a peptide specific for CD11c, preferably a peptide selected from a peptide comprising an amino acid sequence of SEQ ID No.18, 19, 20, 21, 22, 23 or 57, b) a scFv specific for DEC-205, preferably a scFv selected from a scFv comprising an amino acid sequence of SEQ ID No.24, 25, 26, 27, 28, 29 or 30, and c) a polypeptide specific for DC-SIGN, preferably a polypeptide comprising an amino acid sequence of SEQ ID No.36, 37, or 38. In certain embodiments, the present disclosure relates to a polypeptide specifically binding to an antigen present on dendritic cell, wherein said antigen present on dendritic cell is a human antigen. In certain embodiments, the present disclosure relates to a polypeptide specifically binding to a human antigen present on dendritic cell, wherein said polypeptide specifically binding to said antigen present on dendritic cell is cross-reactive with the mouse orthologue of said antigen. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to a human antigen present on dendritic cells, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to a human antigen present on dendritic cells, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain, wherein said polypeptide specifically binding to said human antigen present on dendritic cells is cross-reactive with the mouse orthologue of said antigen. The recombinant proteins of the present disclosure comprise a polypeptide specifically binding to a human antigen present on dendritic cells, a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and a trimerization domain. Said polypeptide specifically binding to a human antigen present on dendritic cells, said designed ankyrin repeat domain specifically binding to the knob of an adenovirus and said trimerization domain may be fused to the other parts of the recombinant protein in any order. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to a human antigen present on dendritic cells, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain, wherein said recombinant protein comprises from the N- to the C-terminus said polypeptide specifically binding to a human antigen present on dendritic cells, said designed ankyrin repeat domain specifically binding to the knob of an adenovirus and said trimerization domain. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to a human antigen present on dendritic cells, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain, wherein said recombinant protein comprises from the N- to the C-terminus said polypeptide specifically binding to a human antigen present on dendritic cells, said designed ankyrin repeat domain specifically binding to the knob of an adenovirus and said trimerization domain, and wherein said polypeptide specifically binding to a human antigen present on dendritic cells is capable of mediating the transduction of dendritic cells. The recombinant proteins of the present disclosure comprise a designed ankyrin repeat domain which binds to the knob of a virus or adenovirus. It will be appreciated that any designed ankyrin repeat domain with specificity for the knob of a virus or adenovirus may be used within the spirit of the present disclosure. Exemplified herein is a designed ankyrin repeat domain derived from DARPin 1D3 (Proc. Natl. Acad. Sci.110, E869–E877 (2013)). DARPin 1D3 binds to the knob of an adenovirus and comprises the amino acid sequence of SEQ ID No. 2. Used herein is 1D3nc, a derivative of 1D3 containing a stabilized C-cap. It will also be understood that also variants of DARPin 1D3 may be used within the spirit of the present disclosure. In other words, the amino acid sequence of such modified DARPin 1D3 does not need to be identical to that of amino acid sequence of SEQ ID No.2, but may contain amino acids mutations, provided that the function of DARPin 1D3, i.e. binding to the knob of an adenovirus is preserved. Also DARPins different than 1D3, but having the same target specificity, may be used within the scope of the present disclosure. Such new DARPin may for example be selected in a new screening campaign. Also binding entities different than DARPins, i.e. binders based on a different scaffold, but having the same target specificity as 1D3 might be used. Therefore, in certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain. wherein said designed ankyrin repeat domain which binds to the knob of an adenovirus is DARPin 1D3. In certain embodiments, the present disclosure relates to a recombinant protein comprising a recombinant protein comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain. wherein said designed ankyrin repeat domain which binds to the knob of an adenovirus is or is derived from DARPin 1D3. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain. wherein said designed ankyrin repeat domain which binds to the knob of an adenovirus is a variant of DARPin 1D3. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain, wherein said designed ankyrin repeat domain which binds to the knob of an adenovirus comprises the amino acid sequence of SEQ ID No.2. In certain embodiments, the present disclosure relates to a recombinant protein comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain, wherein said designed ankyrin repeat domain which binds to the knob of an adenovirus comprises a variant of the amino acid sequence of SEQ ID No.2. A preferred virus to be used in the context of the present disclosure is adenovirus of serotype 5. Viruses, other than adenoviruses of serotype 5, can however also be used within the spirit of the present disclosure. For example, such viruses can be engineered to carry the knob of an adenovirus of serotype 5. The recombinant protein disclosed herein, in particular, the recombinant protein comprising DARPin 1D3, may then be used with such viruses. Therefore, in certain embodiments the present disclosure provides a recombinant protein comprising: a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain, wherein said designed ankyrin repeat domain binds to the knob of an adenovirus of subtype 5. It will be understood that also other adenoviral serotypes may be used in the spirit of the present disclosure, including human adenovirus serotype C5 (HAdV-C5), HAd2, HAd3, HAdV-B35, HAdV-D26, as well as hybrids thereof. A list of adenoviruses can be found on the website of the Human Adenovirus Working group (http: / / hadvwg.gmu.edu). Also, non-human adenoviruses may be used within the scope of the present disclosure, such as the AstraZeneca vaccine chimpanzee adenovirus Y25 (CHAdY25), or non-human adenoviral vectors were developed from bovine (BAd), canine (CAd), chimpanzee (ChAd), ovine (OAd), porcine (PAd), or fowl (FAd). In certain embodiments, the present disclosure relates to recombinant proteins that comprise a trimerization domain. The trimerization domain is responsible for the formation of trimers. Each monomer of the molecules of the present disclosure comprises a trimerization domain. Principally any trimerization domain may be used, provided it is stable and geometrically fits the knob of the adenovirus used. A preferred trimerization domain is the capsid protein SHP of lambdoid phage 21 (J Mol Biol; 344(1):179-93; PNAS 110(10):E869-77 (2013)). Therefore, in certain embodiments the present disclosure relates to recombinant proteins comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain, wherein said trimerization domain is the capsid protein SHP of lambdoid phage 21. In certain embodiments, the present disclosure relates to recombinant proteins comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain, wherein said trimerization domain is derived from the capsid protein SHP of lambdoid phage 21. In certain embodiments, the present disclosure relates to recombinant proteins comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain, wherein said trimerization domain comprises the amino acid sequence of SEQ ID No.1. Also, other trimerization domains known to the skilled person may be used for the formation or trimers. Without being limited other potential trimerization domains include the trimerization domain involved in collagen folding (Int J Biochem Cell Biol 44:21-32 (2012)), the trimerization domain of T4 phage fibritin (PLoS One 7:e43603 (2012)) or the GCN4-based isoleucine zipper (J Biol Chem 290: 7436- 42 (2015)). The trimerization domain is responsible for the formation of the trimeric adapter molecules. The trimers disclosed herein are extraordinarily stable (J Mol Biol (2004) 344:179-93; PNAS (2013) 110 E869-77). In certain embodiments the trimeric adapter molecules of the present disclosure remain intact in SDS gel electrophoresis. In other embodiments the trimeric adapter molecules are not denatured in SDS gel electrophoresis. In other embodiments the trimeric adapter molecules have a half-life in solution of at least one week, preferably at least two week and even more preferably at least one month. Therefore, in certain embodiments, the present disclosure relates to recombinant proteins comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain, wherein said trimerization domain has a half-life in solution of at least one week, preferably at least two week and even more preferably at least one month. The recombinant protein of the present disclosure may also comprise a flexible linker. If the recombinant protein comprising from the N- to the C-terminus a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain, then said flexible linker is between said polypeptide specifically binding to an antigen present on dendritic cell and said designed ankyrin repeat domain specifically binding to the knob of an adenovirus. Therefore, in certain embodiments the present disclosure relates to a recombinant protein comprising from the N- to the C-terminus a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a flexible linker, c) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus,, and d) a trimerization domain. If the recombinant protein comprising from the N- to the C-terminus a) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, b) a trimerization domain, and c) a polypeptide specifically binding to an antigen present on dendritic cell, then said flexible linker is between said trimerization domain and said a polypeptide specifically binding to an antigen present on dendritic cell. Therefore, in certain embodiments the present disclosure relates to a recombinant protein comprising from the N- to the C-terminus a) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, b) a trimerization domain, c) a flexible linker, and d) a polypeptide specifically binding to an antigen present on dendritic cell. Principally any flexible linker can be used within the spirit of the present disclosure. Certain preferred flexible linkers are glycine-serine linkers. A particularly preferred flexible linker is a (Gly4Ser)4- linker. Therefore, in certain embodiments the present disclosure relates to a recombinant protein comprising from the N- to the C-terminus a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a flexible linker, c) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and d) a trimerization domain, wherein said flexible linker is a glycine-serine linker. In other embodiments the present disclosure relates to a recombinant protein comprising from the N- to the C-terminus a) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, b) a flexible linker, c) a trimerization domain, and d) a polypeptide specifically binding to an antigen present on dendritic cell, wherein said flexible linker is a (Gly4Ser)4-linker. The recombinant protein of the present disclosure may also comprise a short linker. The short linker is located between the designed ankyrin repeat domain which binds to the knob of an adenovirus and the trimerization domain. Therefore, in certain embodiments the present disclosure relates to a recombinant protein comprising from the N- to the C-terminus a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, c) a short linker, and d) a trimerization domain. In other embodiments the present disclosure relates to a recombinant protein comprising from the N- to the C-terminus a) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, b) a short linker, c) a trimerization domain, and d) a polypeptide specifically binding to an antigen present on dendritic cell. The short linker does not necessarily be present. Possible short linkers of the present disclosure are linkers which are no longer than four, no longer than three, no longer than two or only one amino acid long. A preferred short linker is glycine. Another preferred short linker is glycine-alanine. Most preferably the short linker is glycine. In certain embodiments, the present disclosure relates to a trimeric protein comprising three recombinant proteins as described herein above. In certain embodiments, the present disclosure relates to a trimeric protein consisting of three recombinant proteins as described herein above. The recombinant proteins of the present disclosure are encoded by nucleic acids. Vectors comprising these nucleic acids are used to transfect cells which express the recombinant proteins. Therefore, in certain embodiments, the present disclosure relates to a nucleic acid encoding a recombinant protein of the present disclosure. The present disclosure also relates to a nucleic acid encoding a recombinant protein comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain. In other embodiments, the present disclosure relates to a vector comprising a nucleic acid encoding a recombinant protein of the present disclosure. The present disclosure also relates to a vector comprising a nucleic acid encoding a recombinant protein comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain, In another embodiments, the present disclosure relates to an adenovirus comprising a nucleic acid encoding a recombinant protein of the present disclosure. In yet another embodiment, the present disclosure relates to an adenovirus comprising a vector comprising a nucleic acid encoding a recombinant protein of the present disclosure. In certain embodiments said adenovirus carries a TAYT mutation. In certain embodiments said adenovirus carries a HVR7 mutation. In certain embodiments, the present disclosure relates to an adenoviral vector comprising a nucleic acid encoding a recombinant protein comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain, In certain embodiments, the present disclosure relates to an a recombinant adenovirus displaying a recombinant protein according or a trimeric protein as disclosed herein. In certain embodiments said adenovirus is of adenovirus serotype 5. In other embodiments said adenovirus comprises a knob of an adenovirus of serotype 5. The recombinant proteins of the present disclosure can be expressed in prokaryotic cells, such as Escherichia coli, and in eukaryotic cells. Preferred eukaryotic cells are CHO cells. Other preferred eukaryotic cells are HEK293 cells, HEK293-T cells, HEK293-F cells, CHO-S cells and Sf9 cells. Therefore, in certain embodiments the present disclosure provides a eukaryotic cell expressing the recombinant protein of the present disclosure. In certain other the present disclosure provides a CHO cell expressing the recombinant protein of the present disclosure. In certain embodiments, the present disclosure relates to a eukaryotic cell expressing a recombinant protein comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain. In certain embodiments, the present disclosure relates to a CHO cell expressing a recombinant protein comprising a) a polypeptide specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain. The recombinant proteins of the present disclosure, the nucleic acids encoding the recombinant proteins and trimeric proteins of the present disclosure, the vectors containing the nucleic acids of the present disclosure and the recombinant adenoviruses containing the recombinant proteins, the nucleic acids or the vectors of the present disclosure have numerous uses, such as the use in an adenoviral delivery system. Therefore, in certain embodiments the present disclosure provides the use of the recombinant proteins of the present disclosure in an adenoviral delivery system. In other embodiments the present disclosure provides the use of the nucleic acids encoding the recombinant proteins of present disclosure in an adenoviral delivery system. In other embodiments the present disclosure provides the use of the vectors containing the nucleic acids of the present disclosure in an adenoviral delivery system. In other embodiments the present disclosure provides the use of the adenoviruses containing the recombinant proteins, the nucleic acids or the vectors of the present disclosure in an adenoviral delivery system. The recombinant proteins of the present disclosure, the nucleic acids encoding the recombinant proteins and trimeric proteins of the present disclosure, the vectors containing the nucleic acids of the present disclosure and the recombinant adenoviruses containing the recombinant proteins, the nucleic acids or the vectors of the present disclosure can also be used for the transduction of dendritic cells. Therefore, in certain embodiments the present disclosure provides the use of the recombinant proteins of the present disclosure for the transduction of dendritic cells. The recombinant proteins of the present disclosure, the nucleic acids encoding the recombinant proteins and trimeric proteins of the present disclosure, the vectors containing the nucleic acids of the present disclosure and the recombinant adenoviruses containing the recombinant proteins, the nucleic acids or the vectors of the present disclosure can also be used in medicine. Therefore, in certain embodiments the present disclosure provides the use of the recombinant proteins of the present disclosure in medicine. In other embodiments the present disclosure provides the use of the nucleic acids encoding the recombinant proteins of the present disclosure in medicine. In other embodiments the present disclosure provides the use of the vectors containing the nucleic acids of the present disclosure in medicine. In other embodiments the present disclosure provides the use of the adenoviruses containing the recombinant proteins, the nucleic acids or the vectors of the present disclosure in medicine. In certain embodiments the present disclosure provides a method to treat a patient, said method comprising administering to a patient in need of a recombinant protein of the present disclosure. In certain embodiments the present disclosure provides a method to treat a patient, said method comprising administering to a patient in need of a nucleic acid encoding a recombinant protein of the present disclosure. In certain embodiments the present disclosure provides a method to treat a patient, said method comprising administering to a patient in need thereof a vector containing a nucleic acid of the present disclosure. In certain embodiments the present disclosure provides a method to treat a patient, said method comprising administering to a patient in need thereof a recombinant adenovirus containing a recombinant protein, a nucleic acid or a vector of the present disclosure. The recombinant proteins of the present disclosure, the nucleic acids encoding the recombinant proteins of the present disclosure, the vectors containing the nucleic acids of the present disclosure, the recombinant adenovirus displaying or containing the recombinant proteins, the nucleic acids or the vectors of the present disclosure, and the eukaryotic cells containing the recombinant adenovirus or set of recombinant adenoviruses of the present disclosure can be used in the treatment or prevention of any disease or disorder. Particularly preferred is the treatment of cancer. Examples Example 1: General experimental procedures Design, expression and purification of retargeting adapters Retargeting modules (scFv, peptides or viral GPs) binding to CD40, CD11c, CD206, DEC205 and DC- SIGN were cloned as mono-adapter or dual-adapter format into the expression plasmid pcDNA3.1. From published full length antibodies, retargeting modules were engineered in the scFv-format (Nterm-VL-(GGGGS)3 [SEQ ID No.58]-VH-Cterm). From published LASV GP (UniProt P08669) either 59- 237 (GP1), or 59-424 (GP1 / GP1), respectively were used as retargeting modules binding to DC-SIGN. The introduced point mutation (M192R) blocks binding of LASV GP1 to LAMP1. iCAM1 (UniProt P13597) 407-421 (loop4) was used as retargeting module binding to CD11c. Flexible linkers to the 1D3nc DARPin, or between the two retargeting modules were in the range of (GGGGS)4 [SEQ ID No. 39]-- (GGGGS)6 [SEQ ID No.40]. The adapter construct contains an N-terminal HSA leader peptide and a C-terminal SHP-domain (leading to trimerization of the protein). The adapters were expressed in CHO-S cells via PEI transfection, using 3x10^6 cells / mL and 5 mg / L PEI mixed with 2.5 mg / L DNA. Cells were incubated at 31°C for 6 days and 180 rpm. Secreted protein of scFv-containing adapters were directly purified by protein L affinity column from the cell-free supernatant. After 10 column volume of wash (PBS, pH 7.4), the one-step gradient elution was executed with elution buffer, 0.1 M citric acid (Merck, pH 2.5). Resulting fractions were neutralized immediately with 1 M Tris (Serva, pH 9.0), followed by SEC polishing (see below). In contrast for secreted protein adapters, the supernatant were dialyzed against 30,000 total volumes of 20mM Tris-HClcontaining 10 mM NaCl (pH 7.2) using dialysis tubings with a molecular weight cut-off (MWCO) of 12–14 kDa at 4°C. During 24 h, the buffer was exchanged three times at a ratio of 1:30. The dialyzed supernatant was loaded on a Mono Q HR 16 / 10 (20ml CV). After 6 CV wash (20mM tris-HCl with 10 mM NaCl), elution was done over 20 CV for 0-25% elution buffer (elution buffer: 20 mM Tris-HCl with 1M NaCl), followed by 100% wash. Correct fractions were determined by SDS-PAGE (silver staining). Final polishing of pooled fractions was done by SEC on a Superdex 200 with on-column buffer exchange to endotoxin-free PBS (Merck Millipore) and then snap- frozen in liquid nitrogen and stored at -20°C until use. Cell lines and primary cells The following cell lines were used: DC2.4 (Merck SCC142, cultured as recommended by Merck), MutuDC (gift by the Acha-Orbea group, University of Geneva), B16-OVA MO4 (Merck SCC420, cultured as recommended by Merck), A549 (ATCC CCL-185), HEK293 (ATCC CRL-1573), 116 (gift by Philip Ng). Primary mouse cells from femur bone marrow of C57BL / 6N mice were cultured and differentiated to murine BMDCs. Human peripheral blood CD14+ monocytes cryopreserved (Zenbio SER-CD14-F) were cultured and differentiated via CellXVivo Human Monocyte-derived DC Differentiation Kit (bio- techne CDK004), CellXVivo Human M1 Macrophage Differentiation Kit (bio-techne CDK012) or CellXVivo Human M2 Macrophage Differentiation Kit (bio-techne CDK013). For receptor staining by flow cytometry, the following antibodies were used: anti-muCD11c (BioLegend clone N418), anti -hCD11c (BioLegend clone Bu15), anti -muDC-SIGN (BioLegend clone MMD3), anti -hDC-SIGN (BioLegend clone 9E9A8), anti-muCD206 (BioLegend clone C068C2), anti- muCD40 (BioLegend clone 3 / 23), anti-muDEC205 (BioLegend clone NLDC-145), anti-muH-2Kb (BioLegend clone AF6-88.5), anti-SIINFEKL bound to muH-2Kb (BioLegend clone 25-D1.16) Plasmid constructions, payload design and virus production The HAdV5HVR7vectors ( “1st generation” vectors) were obtained by cloning the gene of interest into the pAdEasy-1 plasmid system from Agilent Technologies. The gene of interest is encoded under the CMV promotor followed by a SV40 terminator. Virus particles were produced in HEK293 cells and purified by a CsCl gradient. For the mock HAdV5HVR7vector, a gene of interest is missing between the CMV promotor and the SV40 terminator, resulting in final HAdV5HVR7virus particles unable to produce a payload. The HC-HAdV5HVR7vectors ( “gutless” or “high capacity” vectors) were obtained by cloning the gene of interest into the pUniversal plasmids (Mol. Therapy Meth. Clin. Dev.(2021) 20:572-586) and further combined with the pC4HSU plasmid by Gibson assembly. HC-HAdV5HVR7were amplified with the helper virus pmCherryHVR7 containing four mutations into the hypervariable loop 7 of the hexon (I421G, T423N, E424S and L426Y). Virus particles were produced in 116 cells and purified by CsCl gradient. For the payload designs, the invariant chain fused to chicken ovalbumin 242-353 amino acids (“li- OVA.I+II”) was cloned as gene cassette under the CMV promotor followed by the BGH terminator. Alternatively, full length ovalbumin (GenBank: SERPINB14) was cloned as gene cassette under the CMV promotor followed by the BGH terminator. For two pC4HSU constructs, an additional expressing cassette with a cytokine encoded followed downstream of the li-OVA.I+II expression cassette. These cytokines (muIL2v or muIL21) were encoded under the PGK promotor followed by a human ^-globin terminator. This mutated version of muIL2 prevents binding to IL2Rα and has not preferential activation of Treg cells. The murine IL-21 gene sequence was translated from its GenBank entry (GenBank: AF254070.1) and then the payload genes were codon-optimized for mouse expression and synthesized by Twist Bioscience. The muIL2 and muIL21 genes included their native signal sequence. Genomic and infectious particle determination Infectious particles were determined by infectivity assay on A549 cells. HC-HAdV5 genomes were quantified by qPCR with specific primers binding in the encapsulation signal region (5′TGACAATTTTCGCGCGGTTTTAGG-3′ (SEQ ID No.8), 5′-CACTTCCTCTTATTCAGTTTTCCCGC -3′ (SEQ ID No.9)) and a specific double-quenched probe (5′-TGTAGTAAATTTGGGCGTAACCGAGTAAGATTTGGCC- 3′ (SEQ ID No.10)). HAdV5 or HV-impurities in HC-HAdV5 sample were quantified by qPCR with specific primers binding to the hexon encoding region (5′-GAATAACAAGTTTAGAAACCCCACGGTGG-3′ (SEQ ID No.11), 5′-GTTTGACCTTCGACACCTATTTGAATACCC-3′ (SEQ ID No.12)) and a specific double-quenched probe (5′-TGACATCCGCGGCGTGCTGGACAGG-3′ (SEQ ID No.13)). All reactions were performed using the PrimeTime gene expression master mix (Integrated DNA Technologies, 105571) and the reaction signals were normalized to the passive dye rhodamine-X (ROX). Transduction experiments cell culture For screening and characterization of adapter proteins, 2x105cells / well (DC2.4, MutuDC or primary cells) were seeded in a 96-well format 6 hours prior to the experiment. Reporter virus was incubated with trimeric adapter protein in a ratio of 1 infectious particle to 600-1200 fold adapter protein. Virus and adapter protein were incubated for 2 hours on ice and then diluted with PBS (pH 7.4) and added to the cells in the corresponding MOI (multiplicity of infection). After total incubation for 42 hours on cells, cells were washed with PBS. In case of transduction with the encoded reporter protein ffLuciferase, passive lysis buffer (Promega, E194A) was added. After 15min of incubation at RT, luciferase activity of the lysate was determined by a luciferase assay (Promega, E1500) according to the manufacturer’s instructions. In case of transduction with the encoded reporter protein tdTomato, cells were detached from the plate with Trypsin or Accutase and resuspended in PBS+1%BSA+0.1%Na- azide. The percentage of fluorescent positive cells were directly measured by flow cytometry (FACSymphony 5L). The following reporter viruses were used in this assay: HAdV5HVR7, encoding tdTomato under the CMV promotor; HAdV5HVR7, encoding ffLuciferase-IRES-GFP under the CMV promotor. For uptake blocking, anti-muCD11c antibodies (Biolegend clone N418) and anti-muDC-SIGN (Biolegend clone MMD3) were added in a final concentration of 5 µg / mL. As positive uptake control, human lactoferrin was preincubated at a concentration of 1 µM with the virus sample for 2 hours on ice, before dilution and addition to the cells. For blocking the natural uptake that occurs by binding of CAR to the HAdV5 knob, a a-non binding DARPin adapter (E2_5-1D3nc_SHP) was used which covers the CAR epitope on the fiber knob. In vivo biodistribution and tumor vaccination study (B16-OVA MO4) C57BL / 6N WT mice were injected subcutaneously into the right hock with HAdV5HVR7, encoding ffLuciferase-IRES-GFP under the CMV promotor, that has been previously incubated for 1 hour at 4°C either with the retargeting anti-DC adapter ( “retargeted”) or without additives (“untargeted”). A total of AdV5 of 3*108i.p. in 50 µL injected was used (infectious particles, determined by A549 cells). After 2 days, from euthanized mice, liver, spleen and popliteal & inguinal lymph nodes were harvested and snap frozen. Frozen tissue was homogenized at 4C (Precellys Evolution homogenizer), followed by tissue lysing by adding passive lysis buffer (Promega, E194A) to a defined amount of tissue homogenate. After 15 min of incubation at RT, luciferase activity was determined from the lysate’s supernatant by a luciferase assay (Promega, E1500) according to the manufacturer’s instructions. Normalization was done by BCA assay (protein content of liquid tissue supernatant) (ThermoScientific REF23252) C57BL / 6N WT mice were injected intravenously with 4.5x105B16-OVA MO4 cells suspended in RPMI medium. Injected B16-OVA MO4 cells were previously co-incubated for 2 days with 10 ng / ml mIFN-γ for better lung colonization. 4 hours post-i.v. injection, a first vaccination was done by subcutaneously injection into the right hock of HAdV5HVR7or HC-HAdV5HVR7. A total of 3*108i.p. or 1*107i.p., respectively, in 50µL was injected, targeted or untargeted virus samples coding for the indicated payloads (li-OVA1+2 with or without mIL2v or mIL21). A 2nd dose of vaccination was given on day14, with a total of 3*108i.p. or 1*107i.p., respectively, in 50 µL which was injected according to treatment group. CD8 T cell depletion was done for one treatment group (targeted HC-HAdV5HVR7, encoding for li-OVA.1+2 + muIL2v) with 0.2 mg i.p. mCD8-mIgG2 (InvivoGen 10354-42-01) per mouse and timepoint. CD8 T cell depletion was done on the day of the vaccination, as well on the previous and following day; in total 6 times per mouse for 2 vaccination injections. At day 21, mice were euthanized and lungs, spleen and blood isolated and stored on ice. Of lungs, the weight was noted and superficial melanoma foci were counted. Of homogenized and single cell lung samples, the melanin content was measured according to Melanin Assay Kit (Fluorometric) (Abnova REFKA6030). Of homogenized and single cell spleen samples (treated with ACK buffer), 1.2x106splenocytes per sample and staining were used for determination of further T cell subpopulations by flow cytometry. The following stainings were used: Live / DEAD fixable blue stain kit (Invitrogen REF L34962) MHC dextramer H-2 Kb SIINFEKL-APC (immudex REF JD2163-APC), mCD3-AF700 (clone 17A2; BioLegend 100215), mCD3-PE (clone 17A2; BioLegend 100206), mCD4-FITC (clone RM4-5; BioLegend 100509), mCD8a-PE (clone KT15; Santa Cruz Biotechnology sc-53473). For the splenocyte stimulation assay, 4x105splenocytes per sample were incubated (in duplicates) in RPMI medium (+P / S, +10%FCS) in a 24 well plate at 37C for 3 days. T cell stimulation by addition of 5 µM OVA 257-264 peptide (InvivoGen vac-sin) was measured by ELISA of secreted mIFN-γ in cell supernatant (Invitrogen REF 88-8314-22). Of mouse blood samples, serum was diluted in PBS pH 7.4 and a-Ovalbumin and a-AdV5 hexon IgG titers were measured by standard ELISA.5ng / µl Ovalbumin or 5 ng / µL AdV5 hexon was coated overnight at 4°C. Blocking was done by Casein blocking buffer (Sigma-Aldrich B6429), 0.05% Tween20 in PBS (pH 7.4) for 1 hour. Sample incubation was done for 1 hour. The detection antibody was anti-Mouse IgG (H+L)-HRP (ThermoScientific 31438) with a TMB substrate kit (ThermoScientific 34021). As IgG reference mouse anti-ovalbumin antibody clone TOSGAA1 (BioLegend 520401) or mouse a-adenovirus hexon antibody (BioRad 0400-0063) were used as standard protein. Example 2: Generation of DARPins adapters targeting dendritic cells Various potentially useful targeting domains were tested as trimeric DARPin adapters for their capability to target adenoviruses to dendritic cells. Targeting domains tested include moieties targeting CD40, CD11c, CD206, DEC-205 and DC-SIGN. - a scFv against CD40 (US 9,676,861) - a peptide specific for CD11c (Int J Cancer (2011) 129: 1391-403) - a peptide specific for CD206 (Sci Transl Med (2020);12(530):eaax6337) - a scFv against DEC-205 (WO2019 / 082208) - a glycoprotein from Lassa mammarenavirus (LASV) specific for DC-SIGN. All constructs were generated as described in Example 1. Sequences of the DC targeting domains of are shown in the following table. Table 1: SEQ ID No. Description Amino acid sequence 14 Soluble murine GPGSMQRGDEDPQIAAHVVSEANSNAASVLQWAKKGYYTMKSNLV CD40L MLENGKQLTVKREGLYYVYTQVTFCSNREPSSQRPFIVGLWLKPSSGSE RILLKAANTHSSSQLCEQQSVHLGGVFELQAGASVFVNVTEASQVIHR VGFSSFGLLKL 15 Anti-CD40 scFv GPGSDIVMTQTPSSASEPVGGTVTIKCQASQSISSRLAWYQQKPGQPP (R9) KLLIYRASTLASGVSSRFKGSGSGTQFTLTISDLECADAATYYCQCTGYTI SWPFGGGTEVVVKGGGGSGGGGSGGGGSQSLEESGGDLVKPGASLT LTCTASRFSFSSTYMCWVRQAPGKGLEWIACTYTGSSGGTYYASWAK GRFTISQTSSTTVTLQLTGLTPADTATYFCARPDVGFDFAINFWGPGTL VTVSSKL 16 Anti-CD40 scFv GPGSAYDMTQTPASVEVAVGGTVTINCQASQSISSYLYWYQQKPGQP (R33) PKLLIYDASKLASGVPSRFKGSGSGTQFTLTITGVECADAATYYCQQGYS HINVDNIFGGGTEVVVKGGGGSGGGGSGGGGSQSLEESGGDLVKPG ASLTLTCTASGFSFSSSYWICWVRQAPGKGLEWIACINTGSSVTTVYAR WAKGRFTISKASSTTVTLQMTSLTAADTATYFCARYIIPGYNFNLWGPG TLVTVSSKL 17 Anti-CD40 scFv GPGSAQVLTQTPSPVSAPVGGTVTINCQSSQNVLINNRLAWYQQKPG (19-21) QPPKLLIYDASKLASGVPSRFKGSGSGTQFTLTISGVQCDDAATYYCQA GYSSGDGNAFGGGTEVVVKGGGGSGGGGSGGGGSQSLEESGGRLVT PGTPLTLTCTVSGFDLSSNAMNWVRQAPGKGLEWIGYITISGSAGYAS WAKGRFTISKTSTTVDLKISSPTTEDTATYFCARGYNTMAIWGPGTLVT VSSKL 18 Anti-CD11c scFv GPGSDIQMTQSPSSLPASLGDRVTIHCQASQDISNYLTWYQQKPGKA (N418) PKLLIYETNKLADGVPSRFSGSGSGRDYSFTISSLESEDVGSYYCQHYYDY PRTFGPGTKLEIKRAAGGGGSGGGGSGGGGSQVKLQESGGGLVQPG RSLKLSCAASGFTFSNSGMHWIRQSPTKGLEWVASISPSGGTTYYRDS VKGRFTFSRDNAKSTLYLQMDSLRSEDTATYYSATDSGHGYTYFDYWG QGTTVTVSSKL 19 Anti-CD11c GPGSCLNCSNCPQPQNSSLRTPLRQGCKL peptide (p17 cycl) 20 Anti-CD11c GPGSLNCSNCPQPQNSSLRTPLRQGKLG peptide (p17) Anti-CD11c GPGSCSLERFTGLDLANVTLTYEFAAGPRDFWQPCKL peptide (p18 cycl) Anti-CD11c GPGSSLERFTGLDLANVTLTYEFAAGPRDFWQPKL peptide (p18) Anti-CD11c GPGSGRWSGWPADLKL peptide (p30) Anti-DEC205 GPGSDIQMTQSPSFLSTSLGNSITITCHASQNIKGWLAWYQQKSGNAP scFV (NLDC) QLLIYKASSLQSGVPSRFSGSGSGTDYIFTISNLQPEDIATYYCQHYQSFP WTFGGGTKLEIKRAAGGGGSGGGGSGGGGSEVKLQQSGTEVVKPGA SVKLSCKASGYIFTSYDIDWVRQTPEQGLEWIGWIFPGEGSTEYNEKFK GRATLSVDKSSSTAYMELTRLTSEDSAVYFCARGDYYRRYFDLWGQGT TVTVSSKL Anti-DEC205 GPGSASQVQLQQSGPGLVKPSQTLSLTCAISGDSVSTFNIAWNWIRQS scFV (scFv12) PSRGLEWLGRTYYRSKWYTDFAVSVKSRTTINPDTFKNHFSLQLNSVTP EDTAVYYCARGQHSSFDRWGQGTPVTVSSASTKGPSGILGGGGSGGG GSGGGGSQPVLTQPPSASGTPGQRVTISCSGSSSNIGSNYVYWYQQLP GTAPKLPIYRNNQRPSGVPDRFSGSKSGTSASLAISGPRSEDEAAYYCA AWDDSLSGYAVFGGGTQLTVLSGILEQKLISEEDLKL Anti-DEC205 GPGSASQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNTAAWNWIRQ scFV (scFv37) SPWRGLEWLGRTYYRSQWNTDYAVSVKSRITINPDTSKNQFSLQLNSV TPEDTAVYYCARGWSGMDVWGQGTTVTVSSGSASAPTGILGGGGSG GGGSGGGGSEIVMTQSPGTLSLSPGERATLSCRASQSVSSNYLAWYQ QKPGQAPRLVIYGASSRASGIPDRFSGSGSGTDFTLTISRLEPEDFAVYY CQQYGSSHSIRFGQGTQLEIKSGILEQKLISEEDLKL Anti-DEC205 GPGSASQVQLQQSGPGLVRPSQTLSLTCDISGDSVSRDTAAWNWVR scFV (scFv39) QSPWRGLEWLGRTYYRSEWKTDYAVSLKSRITINPDTSKSQFSLQLNSV TPEDTAVYYCARGWSGMDVWGQGTTVTVSAGSASAPTGILGGGGS GGGGSGGGGSEIVMTQSPGTLSLSPGERATLSCRASQSVSSNYLAWY QQKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVY YCQQYGSSPSISFGQGTRLEIKSGILEQKLISEEDLKL Anti-DEC205 GPGSASQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQ scFV (scFv42) SPSRGLEWLGRTYYRSKWYNDYAVSVKSRITIKPDTSKNQFSLQLNSVT PDDTAVYYCARSASYQEYLQSWGQGTLVTVSSGILGGGGSGGGGSGG GGSEIVLTQSPGTLSVSPGERATLSCRASQSVSRNLAWFQQKPGQAPR LLMYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAAYYCQQYDQW PRTFGQGTKVEIKSGILEQKLISEEDLKL Anti-DEC205 GSASQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWLRQSP scFV (scFv83) SGGLDWLGRTYYGSKWNNDYAASVKGRMTITPDTSKNQFSLQLNSVT PDDTAVYYCARTRGGYHYDYWGQGTLVTVSSGILGGGGSGGGGSGG GGSNFMLTQPHSVSQSPGETVTISCTGSSGSIASNFVQWYQQRPGTLP TTVIFDNDKRPSGVPDRVSGSVDSSSNSASLTISGLTAGDEADYYCQYC GNNVRVFGGGTQLTVLSGILEQKLISEEDLKL Anti-DEC205 GPGSASQVQLQQSGPGLVRPSQTLSLTCAISGDSVSRDTAAWNWVR scFV (scFv95) QSPWGGLEWLGRTYYRSEWNTDYAVSLKSRMTITPDTSKSQFSLQLN SVTPEDTAVYYCARGWSGMDVWGHGTTVTVSAGSASAPTGILGGGG SGGGGSGGGGSEIVMTQSPGTPFLSPGERATLSCRASQSVSSNYSAW YQQKPGQAPRLVIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDYAV YYCQQYGSSPLISFGQGTRLEIKSGILEQKLISEEDLKL 31 Anti-CD206 GPGSKFRKAFKRFFKL peptide (RP- 182) 32 Anti-CD206 GPGSFFKKFFKKFKKL peptide (RP- 185) 33 Anti-CD206 GPGSKARKAAKRAFKL peptide (RP- 426) 34 Anti-CD206 GPGSCSPGAKKL peptide (mUNO) 35 Anti-CD206 GPGSCSPGAKVRCKL peptide (UNO) 36 Anti-DCSIGN GPGSTSLYKGVYELQTLELNMETLNMTMPLSCTKNNSHHYIMVGNET (LASV GLELTLTNTSIINHKFCNLSDAHKKNLYDHALMSIISTFHLSIPNFNQYEA MSCDFNGGKISVQYNLSHSYAGDAANHCGTVANGVLQTFRRMAWG GP1(M192R)) GSYIALDSGRGNWDCIMTSYQYLIIQNTTWEDHCQFSRPSKL 37 Anti-DCSIGN GPGSTSLYKGVYELQTLELNMETLNMTMPLSCTKNNSHHYIMVGNET (LASV GLELTLTNTSIINHKFCNLSDAHKKNLYDHALMSIISTFHLSIPNFNQYEA MSCDFNGGKISVQYNLSHSYAGDAANHCGTVANGVLQTFRRMAWG GP1(M192R)GP GSYIALDSGRGNWDCIMTSYQYLIIQNTTWEDHCQFSRPSPIGYLGLLS 2) QRTRDIYISRRLLGTFTWTLSDSEGKDTPGGYCLTRWMLIEAELKCFGN TAVAKCNEKHDEEFCDMLRLFDFNKQAIQRLKAEAQMSIQLINKAVN ALINDQLIMKNHLRDIMGIPYCNYSKYWYLNHTTTGRTSLPKCWLVSN GSYLNETHFSDDIEQQADNMITEMLQKEYMERQGKL 38 Anti-DCSIGN GPGSTSLYKGVYELQTLELNMETLNMTMPLSCTKNNSHHYIMVGNET (LASV GP1 wt) GLELTLTNTSIINHKFCNLSDAHKKNLYDHALMSIISTFHLSIPNFNQYEA MSCDFNGGKISVQYNLSHSYAGDAANHCGTVANGVLQTFMRMAW GGSYIALDSGRGNWDCIMTSYQYLIIQNTTWEDHCQFSRPSKL All mono-module adapters tested had the following composition (from N- to C- terminus): - a DC targeting domain (any one of SEQ ID NO.s 14-35), - a (G4S)4 linker (GGGGSGGGGSGGGGSGGGGS (SEQ ID No.39)), - DARPin 1D3nc (SEQ ID No.2), and - a trimerization domain (SEQ ID No.1). Example 3: Transduction of dendritic cell line utilizing mono-module DARPin adapters DARPin adapters comprising the targeting domains shown in Table 1 were tested for their capability to increase the transduction rate of adenoviruses captured with the respective DARPin adapters to dendritic cells. All adapters led to some, but no significant increase of the transduction rate, with the effect being most pronounced with certain anti-CD11c peptides, anti-DEC-205-scFv`s and the anti-DC-SIGN glycopeptide from LASV. See Figure 1. Example 4: Transduction of dendritic cell line utilizing dual-module DARPin adapters In a next experiment it was evaluated, if dual-module DARPin adapters could increase transduction efficiency in dendritic cells even more. Dual-module adapters carry two targeting domains in tandem, separated by a linker (either a (G4S)4linker (GGGGSGGGGSGGGGSGGGGS (SEQ ID No.39)) or a (G6S)6linker (GGGGSGGGGSGGGGSGGGGSGGGGSGGGGS (SEQ ID No.40)). Targeting domains were tested in various N- to C-terminal order and with various linkers. In this experiment also an additional anti-CD11c targeting unit was used, namely the D4 loop of iCAM1 with the following amino acid sequence: LGNWTWQEGSQQTLK (SEQ ID No.57) The following dual-module DARPin adapters were tested targeting DEC205 and CD11c. Table 2: No Description Amino acid sequence 26DEC205ASQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKW (scFv42)- (GGGGS)6- YNDYAVSVKSRITIKPDTSKNQFSLQLNSVTPDDTAVYYCARSASYQEYLQSWGQGTLVTVSS CD11c(p17) GILGGGGSGGGGSGGGGSEIVLTQSPGTLSVSPGERATLSCRASQSVSRNLAWFQQKPGQA PRLLMYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAAYYCQQYDQWPRTFGQGTKVEI KSGILEQKLISEEDLGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSLNCSNCPQPQNSSLRT PLRQGKLGGGGSGGGGSGGGGSGGGGSRSDLGKKLLEAARAGQDDEVRILMANGADANA YDHYGRTPLHMAAAVGHLEIVEVLLRNGADVNAVDTNGTTPLHLAASLGHLEIVEVLLKYGA DVNAKDATGITPLYLAAYWGHLEIVEVLLKHGADVNAQDKFGKTPFDLAIDNGNEDIAEVLQ GVRIFAGNDPAHTATGSSGISSPTPALTPLMLDEATGKLVVWDGQKAGSAVGILVLPLEGTET ALTYYKSGTFATEAIHWPESVDEHKKANAFAGSALSHAALP (SEQ ID No.41)DEC205ASQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKW (scFv42)- (GGGGS)4- YNDYAVSVKSRITIKPDTSKNQFSLQLNSVTPDDTAVYYCARSASYQEYLQSWGQGTLVTVSS CD11c(p17) GILGGGGSGGGGSGGGGSEIVLTQSPGTLSVSPGERATLSCRASQSVSRNLAWFQQKPGQA PRLLMYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAAYYCQQYDQWPRTFGQGTKVEI KSGILEQKLISEEDLGGGGSGGGGSGGGGSGGGGSLNCSNCPQPQNSSLRTPLRQGKLGGG GSGGGGSGGGGSGGGGSRSDLGKKLLEAARAGQDDEVRILMANGADANAYDHYGRTPLH MAAAVGHLEIVEVLLRNGADVNAVDTNGTTPLHLAASLGHLEIVEVLLKYGADVNAKDATGI TPLYLAAYWGHLEIVEVLLKHGADVNAQDKFGKTPFDLAIDNGNEDIAEVLQGVRIFAGNDP AHTATGSSGISSPTPALTPLMLDEATGKLVVWDGQKAGSAVGILVLPLEGTETALTYYKSGTFA TEAIHWPESVDEHKKANAFAGSALSHAALP (SEQ ID No.42)DEC205ASQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKW (scFv42)- (GGGGS)6- YNDYAVSVKSRITIKPDTSKNQFSLQLNSVTPDDTAVYYCARSASYQEYLQSWGQGTLVTVSS CD11c(p30) GILGGGGSGGGGSGGGGSEIVLTQSPGTLSVSPGERATLSCRASQSVSRNLAWFQQKPGQA PRLLMYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAAYYCQQYDQWPRTFGQGTKVEI KSGILEQKLISEEDLGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGRWSGWPADLKLGG GGSGGGGSGGGGSGGGGSRSDLGKKLLEAARAGQDDEVRILMANGADANAYDHYGRTPL HMAAAVGHLEIVEVLLRNGADVNAVDTNGTTPLHLAASLGHLEIVEVLLKYGADVNAKDATG ITPLYLAAYWGHLEIVEVLLKHGADVNAQDKFGKTPFDLAIDNGNEDIAEVLQGVRIFAGNDP AHTATGSSGISSPTPALTPLMLDEATGKLVVWDGQKAGSAVGILVLPLEGTETALTYYKSGTFA TEAIHWPESVDEHKKANAFAGSALSHAALP (SEQ ID No.43)DEC205ASQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKW (scFv42)- (GGGGS)4- YNDYAVSVKSRITIKPDTSKNQFSLQLNSVTPDDTAVYYCARSASYQEYLQSWGQGTLVTVSS CD11c(p30) GILGGGGSGGGGSGGGGSEIVLTQSPGTLSVSPGERATLSCRASQSVSRNLAWFQQKPGQA PRLLMYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAAYYCQQYDQWPRTFGQGTKVEI KSGILEQKLISEEDLGGGGSGGGGSGGGGSGGGGSGRWSGWPADLKLGGGGSGGGGSGG GGSGGGGSRSDLGKKLLEAARAGQDDEVRILMANGADANAYDHYGRTPLHMAAAVGHLEI VEVLLRNGADVNAVDTNGTTPLHLAASLGHLEIVEVLLKYGADVNAKDATGITPLYLAAYWG HLEIVEVLLKHGADVNAQDKFGKTPFDLAIDNGNEDIAEVLQGVRIFAGNDPAHTATGSSGIS SPTPALTPLMLDEATGKLVVWDGQKAGSAVGILVLPLEGTETALTYYKSGTFATEAIHWPESV DEHKKANAFAGSALSHAALP (SEQ ID No.44) CD11c(p17)- LNCSNCPQPQNSSLRTPLRQGGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSASQVQLQ (GGGGS)6- QSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSV DEC205 KSRITIKPDTSKNQFSLQLNSVTPDDTAVYYCARSASYQEYLQSWGQGTLVTVSSGILGGGGS (scFv42) GGGGSGGGGSEIVLTQSPGTLSVSPGERATLSCRASQSVSRNLAWFQQKPGQAPRLLMYGA STRATGIPARFSGSGSGTEFTLTISSLQSEDFAAYYCQQYDQWPRTFGQGTKVEIKSGILEQKLI SEEDLKLGGGGSGGGGSGGGGSGGGGSRSDLGKKLLEAARAGQDDEVRILMANGADANAY DHYGRTPLHMAAAVGHLEIVEVLLRNGADVNAVDTNGTTPLHLAASLGHLEIVEVLLKYGAD VNAKDATGITPLYLAAYWGHLEIVEVLLKHGADVNAQDKFGKTPFDLAIDNGNEDIAEVLQG VRIFAGNDPAHTATGSSGISSPTPALTPLMLDEATGKLVVWDGQKAGSAVGILVLPLEGTETA LTYYKSGTFATEAIHWPESVDEHKKANAFAGSALSHAALP (SEQ ID No.45) CD11c(p17)- LNCSNCPQPQNSSLRTPLRQGGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSASQVQLQ (GGGGS)4- QSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSV DEC205 KSRITIKPDTSKNQFSLQLNSVTPDDTAVYYCARSASYQEYLQSWGQGTLVTVSSGILGGGGS (scFv42) GGGGSGGGGSEIVLTQSPGTLSVSPGERATLSCRASQSVSRNLAWFQQKPGQAPRLLMYGA STRATGIPARFSGSGSGTEFTLTISSLQSEDFAAYYCQQYDQWPRTFGQGTKVEIKSGILEQKLI SEEDLKLGGGGSGGGGSGGGGSGGGGSRSDLGKKLLEAARAGQDDEVRILMANGADANAY DHYGRTPLHMAAAVGHLEIVEVLLRNGADVNAVDTNGTTPLHLAASLGHLEIVEVLLKYGAD VNAKDATGITPLYLAAYWGHLEIVEVLLKHGADVNAQDKFGKTPFDLAIDNGNEDIAEVLQG VRIFAGNDPAHTATGSSGISSPTPALTPLMLDEATGKLVVWDGQKAGSAVGILVLPLEGTETA LTYYKSGTFATEAIHWPESVDEHKKANAFAGSALSHAALP (SEQ ID No.46) CD11c(p30)- GRWSGWPADLGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSASQVQLQQSGPGLVKPS (GGGGS)6- QTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITIKPDTS DEC205 KNQFSLQLNSVTPDDTAVYYCARSASYQEYLQSWGQGTLVTVSSGILGGGGSGGGGSGGGG (scFv42) SEIVLTQSPGTLSVSPGERATLSCRASQSVSRNLAWFQQKPGQAPRLLMYGASTRATGIPARF SGSGSGTEFTLTISSLQSEDFAAYYCQQYDQWPRTFGQGTKVEIKSGILEQKLISEEDLKLGGG GSGGGGSGGGGSGGGGSRSDLGKKLLEAARAGQDDEVRILMANGADANAYDHYGRTPLH MAAAVGHLEIVEVLLRNGADVNAVDTNGTTPLHLAASLGHLEIVEVLLKYGADVNAKDATGI TPLYLAAYWGHLEIVEVLLKHGADVNAQDKFGKTPFDLAIDNGNEDIAEVLQGVRIFAGNDP AHTATGSSGISSPTPALTPLMLDEATGKLVVWDGQKAGSAVGILVLPLEGTETALTYYKSGTFA TEAIHWPESVDEHKKANAFAGSALSHAALP (SEQ ID No.47) CD11c(p30)- GRWSGWPADLGGGGSGGGGSGGGGSGGGGSASQVQLQQSGPGLVKPSQTLSLTCAISGD (GGGGS)4- SVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITIKPDTSKNQFSLQLNSV DEC205 TPDDTAVYYCARSASYQEYLQSWGQGTLVTVSSGILGGGGSGGGGSGGGGSEIVLTQSPGTL (scFv42) SVSPGERATLSCRASQSVSRNLAWFQQKPGQAPRLLMYGASTRATGIPARFSGSGSGTEFTLT ISSLQSEDFAAYYCQQYDQWPRTFGQGTKVEIKSGILEQKLISEEDLKLGGGGSGGGGSGGGG SGGGGSRSDLGKKLLEAARAGQDDEVRILMANGADANAYDHYGRTPLHMAAAVGHLEIVE VLLRNGADVNAVDTNGTTPLHLAASLGHLEIVEVLLKYGADVNAKDATGITPLYLAAYWGHLE IVEVLLKHGADVNAQDKFGKTPFDLAIDNGNEDIAEVLQGVRIFAGNDPAHTATGSSGISSPT PALTPLMLDEATGKLVVWDGQKAGSAVGILVLPLEGTETALTYYKSGTFATEAIHWPESVDEH KKANAFAGSALSHAALP (SEQ ID No.48) CD11c(iCAM- LGNWTWQEGSQQTLKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSASQVQLQQSGP 1_D4loop)- GLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRIT (GGGGS)6- IKPDTSKNQFSLQLNSVTPDDTAVYYCARSASYQEYLQSWGQGTLVTVSSGILGGGGSGGGG DEC205 SGGGGSEIVLTQSPGTLSVSPGERATLSCRASQSVSRNLAWFQQKPGQAPRLLMYGASTRAT (scFv42) GIPARFSGSGSGTEFTLTISSLQSEDFAAYYCQQYDQWPRTFGQGTKVEIKSGILEQKLISEEDL KLGGGGSGGGGSGGGGSGGGGSRSDLGKKLLEAARAGQDDEVRILMANGADANAYDHYG RTPLHMAAAVGHLEIVEVLLRNGADVNAVDTNGTTPLHLAASLGHLEIVEVLLKYGADVNAK DATGITPLYLAAYWGHLEIVEVLLKHGADVNAQDKFGKTPFDLAIDNGNEDIAEVLQGVRIFA GNDPAHTATGSSGISSPTPALTPLMLDEATGKLVVWDGQKAGSAVGILVLPLEGTETALTYYK SGTFATEAIHWPESVDEHKKANAFAGSALSHAALP (SEQ ID No.49) CD11c(iCAM- LGNWTWQEGSQQTLKGGGGSGGGGSGGGGSGGGGSASQVQLQQSGPGLVKPSQTLSLT 1_D4loop)- CAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITIKPDTSKNQFSL (GGGGS)4- QLNSVTPDDTAVYYCARSASYQEYLQSWGQGTLVTVSSGILGGGGSGGGGSGGGGSEIVLT DEC205(scFv QSPGTLSVSPGERATLSCRASQSVSRNLAWFQQKPGQAPRLLMYGASTRATGIPARFSGSGS 42) GTEFTLTISSLQSEDFAAYYCQQYDQWPRTFGQGTKVEIKSGILEQKLISEEDLKLGGGGSGGG GSGGGGSGGGGSRSDLGKKLLEAARAGQDDEVRILMANGADANAYDHYGRTPLHMAAAV GHLEIVEVLLRNGADVNAVDTNGTTPLHLAASLGHLEIVEVLLKYGADVNAKDATGITPLYLAA YWGHLEIVEVLLKHGADVNAQDKFGKTPFDLAIDNGNEDIAEVLQGVRIFAGNDPAHTATGS SGISSPTPALTPLMLDEATGKLVVWDGQKAGSAVGILVLPLEGTETALTYYKSGTFATEAIHWP ESVDEHKKANAFAGSALSHAALP (SEQ ID No.50)CD11c(p17)-GPGSLNCSNCPQPQNSSLRTPLRQGGGGGSGGGGSGGGGSGGGGSLNCSNCPQPQNSSLR (GGGGS)4- CD11c(p17) TPLRQGKLGGGGSGGGGSGGGGSGGGGSRSDLGKKLLEAARAGQDDEVRILMANGADAN AYDHYGRTPLHMAAAVGHLEIVEVLLRNGADVNAVDTNGTTPLHLAASLGHLEIVEVLLKYG ADVNAKDATGITPLYLAAYWGHLEIVEVLLKHGADVNAQDKFGKTPFDLAIDNGNEDIAEVL QGVRIFAGNDPAHTATGSSGISSPTPALTPLMLDEATGKLVVWDGQKAGSAVGILVLPLEGTE TALTYYKSGTFATEAIHWPESVDEHKKANAFAGSALSHAALP (SEQ ID No.51) CD11c(p30)- GRWSGWPADLGGGGSGGGGSGGGGSGGGGSASQVQLQQSGPGLVKPSQTLSLTCAISGD (GGGGS)4- SVSSNTAAWNWIRQSPWRGLEWLGRTYYRSQWNTDYAVSVKSRITINPDTSKNQFSLQLNS DEC205 VTPEDTAVYYCARGWSGMDVWGQGTTVTVSSGSASAPTGILGGGGSGGGGSGGGGSEIV (scFv37) MTQSPGTLSLSPGERATLSCRASQSVSSNYLAWYQQKPGQAPRLVIYGASSRASGIPDRFSGS GSGTDFTLTISRLEPEDFAVYYCQQYGSSHSIRFGQGTQLEIKSGILEQKLISEEDLKLGGGGSG GGGSGGGGSGGGGSRSDLGKKLLEAARAGQDDEVRILMANGADANAYDHYGRTPLHMAA AVGHLEIVEVLLRNGADVNAVDTNGTTPLHLAASLGHLEIVEVLLKYGADVNAKDATGITPLYL AAYWGHLEIVEVLLKHGADVNAQDKFGKTPFDLAIDNGNEDIAEVLQGVRIFAGNDPAHTAT GSSGISSPTPALTPLMLDEATGKLVVWDGQKAGSAVGILVLPLEGTETALTYYKSGTFATEAIH WPESVDEHKKANAFAGSALSHAALP (SEQ ID No.52) 38CD11c(p30)- GRWSGWPADLGGGGSGGGGSGGGGSGGGGSASQVQLQQSGPGLVRPSQTLSLTCDISGD (GGGGS)4- SVSRDTAAWNWVRQSPWRGLEWLGRTYYRSEWKTDYAVSLKSRITINPDTSKSQFSLQLNS DEC205 VTPEDTAVYYCARGWSGMDVWGQGTTVTVSAGSASAPTGILGGGGSGGGGSGGGGSEIV (scFv39) MTQSPGTLSLSPGERATLSCRASQSVSSNYLAWYQQKPGQAPRLLIYGASSRATGIPDRFSGS GSGTDFTLTISRLEPEDFAVYYCQQYGSSPSISFGQGTRLEIKSGILEQKLISEEDLKLGGGGSGG GGSGGGGSGGGGSRSDLGKKLLEAARAGQDDEVRILMANGADANAYDHYGRTPLHMAAA VGHLEIVEVLLRNGADVNAVDTNGTTPLHLAASLGHLEIVEVLLKYGADVNAKDATGITPLYLA AYWGHLEIVEVLLKHGADVNAQDKFGKTPFDLAIDNGNEDIAEVLQGVRIFAGNDPAHTATG SSGISSPTPALTPLMLDEATGKLVVWDGQKAGSAVGILVLPLEGTETALTYYKSGTFATEAIHW PESVDEHKKANAFAGSALSHAALP (SEQ ID No.53) 39CD11cLGNWTWQEGSQQTLKGGGGSGGGGSGGGGSGGGGSASQVQLQQSGPGLVKPSQTLSLT (iCAM1 CAISGDSVSSNTAAWNWIRQSPWRGLEWLGRTYYRSQWNTDYAVSVKSRITINPDTSKNQF D4loop)- SLQLNSVTPEDTAVYYCARGWSGMDVWGQGTTVTVSSGSASAPTGILGGGGSGGGGSGG (GGGGS)4- GGSEIVMTQSPGTLSLSPGERATLSCRASQSVSSNYLAWYQQKPGQAPRLVIYGASSRASGIP DEC205 DRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSHSIRFGQGTQLEIKSGILEQKLISEEDLKLG (scFv37) GGGSGGGGSGGGGSGGGGSRSDLGKKLLEAARAGQDDEVRILMANGADANAYDHYGRTP LHMAAAVGHLEIVEVLLRNGADVNAVDTNGTTPLHLAASLGHLEIVEVLLKYGADVNAKDAT GITPLYLAAYWGHLEIVEVLLKHGADVNAQDKFGKTPFDLAIDNGNEDIAEVLQGVRIFAGND PAHTATGSSGISSPTPALTPLMLDEATGKLVVWDGQKAGSAVGILVLPLEGTETALTYYKSGTF ATEAIHWPESVDEHKKANAFAGSALSHAALP (SEQ ID No.54) 40CD11cLGNWTWQEGSQQTLKGGGGSGGGGSGGGGSGGGGSASQVQLQQSGPGLVRPSQTLSLT (iCAM1 CDISGDSVSRDTAAWNWVRQSPWRGLEWLGRTYYRSEWKTDYAVSLKSRITINPDTSKSQF D4loop)- SLQLNSVTPEDTAVYYCARGWSGMDVWGQGTTVTVSAGSASAPTGILGGGGSGGGGSGG (GGGGS)4- GGSEIVMTQSPGTLSLSPGERATLSCRASQSVSSNYLAWYQQKPGQAPRLLIYGASSRATGIP DEC205 DRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPSISFGQGTRLEIKSGILEQKLISEEDLKLGG (scFv39) GGSGGGGSGGGGSGGGGSRSDLGKKLLEAARAGQDDEVRILMANGADANAYDHYGRTPL HMAAAVGHLEIVEVLLRNGADVNAVDTNGTTPLHLAASLGHLEIVEVLLKYGADVNAKDATG ITPLYLAAYWGHLEIVEVLLKHGADVNAQDKFGKTPFDLAIDNGNEDIAEVLQGVRIFAGNDP AHTATGSSGISSPTPALTPLMLDEATGKLVVWDGQKAGSAVGILVLPLEGTETALTYYKSGTFA TEAIHWPESVDEHKKANAFAGSALSHAALP (SEQ ID No.55) Transduction efficiencies were determined at a MOI of 100 and at a MOI of 25. Compared to mono- module DARPin adapters, a slight increase of transduction efficiencies was observed for most of the dual-module adapters tested targeting DEC205 and CD11c. Results for an experiment conducted with an MOI of 100 or 25 is shown in Figure 1. Example 5: Transduction of dendritic cell line utilizing DARPin adapters comprising variants of GP of LASV GP of Lassa mammarenavirus (LASV) is a glycosylated protein, consisting of two main domains, GP1 and GP2 (see Figure 2). In this experiment various versions of GP were compared for their capability to transduce dendritic cells. Tested were a fragment of the wild-type version of GP consisting only the GP1 domain (amino acids 59-237), a full-length version of GP carrying a M192R mutation, and a fragment of GP consisting only the GP1 domain (amino acids 59-237) and carrying the M192R mutation. All adapters tested had the following composition (from N- to C- terminus): - a DC targeting domain (any one of SEQ ID NO.s 36-38), - a (G4S)4 linker (GGGGSGGGGSGGGGSGGGGS (SEQ ID No.39)), - DARPin 1D3nc (SEQ ID No.2), and - a trimerization domain (SEQ ID No.1). Transduction efficiencies were determined at a MOI of 100 and at a MOI of 25. An increase of the transduction efficiency was observed for the adapters carrying GP or variants of GP of LASV. The effect was particularly pronounced for the GP targeting domains carrying the M192R mutation. Results are shown in Figure 3. Example 6: Transduction of dendritic cell lines utilizing dual-module DARPin adapters comprising an anti-anti-CD11c moiety and a M192R variant of GP of LASV Based on the experiments performed so far, the GP domains of LASV carrying a M192R mutation were tested as a dual-module adapter with a construct comprising the loop 4 of iCAM1, i.e. an anti- CD11c moiety. This dual-module DARPin adapters had the following amino acid sequence: LGNWTWQEGSQQTLKGGGGSGGGGSGGGGSGGGGSTSLYKGVYELQTLELNMETLNMTMPLS CTKNNSHHYIMVGNETGLELTLTNTSIINHKFCNLSDAHKKNLYDHALMSIISTFHLSIPNFNQ YEAMSCDFNGGKISVQYNLSHSYAGDAANHCGTVANGVLQTFRRMAWGGSYIALDSGRGNWDCI MTSYQYLIIQNTTWEDHCQFSRPSKLGGGGSGGGGSGGGGSGGGGSRSDLGKKLLEAARAGQDD EVRILMANGADANAYDHYGRTPLHMAAAVGHLEIVEVLLRNGADVNAVDTNGTTPLHLAASLGH LEIVEVLLKYGADVNAKDATGITPLYLAAYWGHLEIVEVLLKHGADVNAQDKFGKTPFDLAIDN GNEDIAEVLQGVRIFAGNDPAHTATGSSGISSPTPALTPLMLDEATGKLVVWDGQKAGSAVGIL VLPLEGTETALTYYKSGTFATEAIHWPESVDEHKKANAFAGSALSHAALP (SEQ ID No. 56) Transduction efficiencies were determined at various MOI (100 or 25). Results are shown in Figure 4. At all MOI`s tested, this dual-module DARPin adapter led to a strong increase of the transduction efficiency in dendritic cell lines .The dual-module adapter (short “ ^-DC adapter”) (SEQ ID No.56) shows on all tested cells a more prominent retargeting effect than its mono-module adapter (short “GP1- adapter”) (retargeting domain SEQ ID No.36). The addition of antibodies to block the entry via CD11c and DC-SIGNs confirms the specific uptake by those named cell surface receptors. Example 7: Retargeting to primary cells at low MOI Next it was tested if the dual-module DARPin adapter of Example 6 is also capable of transducing human or mouse primary dendritic cells (resp. human M1 macrophages) at low MOI Primary cells were isolated or differentiated as described in Example 1. As reporter gene, luciferase was used as described in Example 1. In all experiments the tested adapter led to a strong increase of transduction of dendritic cells. Results for the primary cells are shown in Figures 5, 6 and 7. A strong induction of the transduction of primary dendritic cells was observed. The effect was also observed also at very low MOI`s. Example 8: Lymph node targeting and tumor vaccination efficacy study In this experiment the dual-module DARPin adapters of Examples 6 and 7 were tested in an in vivo tumor vaccination study as described in Example 1. In brief, mice received an s.c. injection of adenoviruses displaying the dual targeting DARPin adapters. In a biodistribution study adenoviruses additionally carried luciferase as a reporter gene. Expression of luciferase after hock injection was determined in lymph nodes, liver and spleen. Results are shown in Figure 8. It was found that the dual-module DARPin adapter led to a significant up-regulation of luciferase expression in lymph nodes by factor 4.5, but not in the liver or the spleen. This confirms that the dual-module DARPin adapter leads to lymph node targeting. The local and direct expression of payloads in the lymph nodes without off-targeting to other tissues (e.g. liver or spleen) is seen as very important for potent therapeutics that may have potential damaging side-effects (e.g. cytokines) when applied systemically. As therapeutic efficacy study we used the lung metastatic model B16-OVA MO4. In the tumor vaccination experiment C57 / BL6 J mice (6-10 weeks old) were injected i.v. with B16-OVA MO4 cells as indicated in Example 1, were grouped and transfected as follows: healthy control: 3-4 Animals mock virus: 5-7 Animals HAdV5 encoding li-OVA.1+2 (untargeted): 7 Animals HAdV5 encoding li-OVA.1+2 (+adapter) : 7 Animals HC-HAdV5 encoding li-OVA.1+2 (untargeted): 7 Animals HC-HAdV5 encoding li-OVA.1+2 (+adapter) : 7 Animals HC-HAdV5 encoding li-OVA.1+2 and mu IL2v (+adapter): 7 Animals HC-HAdV5 encoding li-OVA.1+2 and mu IL21 (+adapter) : 7 Animals Splenocyte staining revealed that mice vaccinated with the dual targeting DARPin adapters led to a significant rise of cytotoxic T cells (factor 3-4) or responsive splenocytes (upon peptide stimulation) (Figure 9). Especially the combination of adapter and co-expression of mu IL2v or mu IL21 directly in lymph nodes lead to the most significant increase. Co-expression of mu IL2v or mu IL21 also led to a significant stimulation of anti-ovalbumin IgG levels by factor of 3 (Figure 10). Mice treated with these adapters also showed a pronounced tumor regression, as measured by dark metastatic foci on the lung surface, melanin content in the lung lysate (as B16 cells produce melanin), as well as the weight of the lungs (Figure 11). These results confirm that it is possible to effectively target adenoviruses to dendritic cells in vivo, and that adenoviruses armed with additional payloads exert a therapeutic effect.

Claims

Claims 1. A recombinant adenovirus displaying a recombinant protein, wherein said recombinant protein increases the transduction of dendritic cells and wherein said recombinant protein comprises a) a binding domain specifically binding to an antigen present on dendritic cell, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain.

2. The recombinant adenovirus according to claim 1, wherein said binding domain specifically binding to an antigen present on dendritic cell is a peptide specific for CD11c.

3. The recombinant adenovirus according to claim 2, wherein said peptide specific for CD11c is selected from a peptide comprising an amino acid sequence of SEQ ID No.18, 19, 20, 21, 22, 23 or 57.

4. The recombinant adenovirus according to claim 1, wherein said binding domain specifically binding to an antigen present on dendritic cell is a scFv specific for DEC-205.

5. The recombinant adenovirus according to claim 4, wherein said scFv specific for DEC-205 is selected from a scFv comprising an amino acid sequence of SEQ ID No.24, 25, 26, 27, 28, 29 or 30.

6. The recombinant adenovirus according to claim 1, wherein said binding domain specifically binding to an antigen present on dendritic cell is a polypeptide specific for DC-SIGN.

7. The recombinant protein according to claim 6, wherein said a polypeptide specific for DC-SIGN is selected from a polypeptide comprising an amino acid sequence of SEQ ID No.36, 37, or 38.

8. The recombinant adenovirus according to any one of the preceding claims, wherein said recombinant protein comprises from the N- to the C-terminus said binding domain specifically binding to an antigen present on dendritic cell, said designed ankyrin repeat domain specifically binding to the knob of an adenovirus and said trimerization domain.

9. The recombinant adenovirus according to any one of the preceding claims, wherein said designed ankyrin repeat domain that specifically binds to the knob of an adenovirus comprises the amino acid sequence of SEQ ID No.2 and / or wherein said trimerization domain comprises the amino acid sequence of SEQ ID No.1.

10. The recombinant adenovirus according to any one of the preceding claims, wherein said recombinant protein comprises a polypeptide comprising the amino acid sequence of any one of SEQ ID Nos.26-40 or 56.

11. A recombinant protein comprising a) a binding domain specifically binding to an antigen present on dendritic cell selected from CD11c, DEC-205 and DC-SIGN, b) a designed ankyrin repeat domain specifically binding to the knob of an adenovirus, and c) a trimerization domain.

12. The recombinant protein according to claim 11, wherein said binding domain specifically binding to an antigen present on dendritic cell is selected from a) a peptide specific for CD11c, preferably a peptide selected from a peptide comprising an amino acid sequence of SEQ ID No.18, 19, 20, 21, 22, 23 or 57, b) a scFv specific for DEC-205, preferably a scFv selected from a scFv comprising an amino acid sequence of SEQ ID No.24, 25, 26, 27, 28, 29 or 30, and c) a polypeptide specific for DC-SIGN, preferably a polypeptide comprising an amino acid sequence of SEQ ID No.36, 37, or 38.

13. A nucleic acid encoding a recombinant protein according to claim 11 or 12.

14. A trimeric protein comprising three recombinant proteins according to claim 11 or 12.

15. The recombinant adenovirus according to any one of claims 1-10, use in the transduction of dendritic cells.

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