Conditional agonists for receptors of the TNF receptor superfamily with a binding site for TRAF2

Abstract

The present invention relates to at least bispecific fusion protein constructs comprising a scaffold domain and binding domains of at least two specificities of which at least one is specific for a member of the tumor necrosis factor (TNF) receptor superfamily (TNFRSF) which contains a binding site for TNF receptor associated factor-2 (TRAF2). These constructs can be used to engage these TNFRSF receptors (TNFRs), for example to trigger the classical and / or alternative NFkappaB signaling pathways in the TNFR expressing cells. The invention also relates to an extendible protein library generated by coexpression of two amino acid chains from two supplemental groups of fusion proteins each composed of a constant scaffolding part and a binding domain enabling interaction with a cell surface- or extracellular matrix exposed protein / molecule enabling the rapid and simple generation of heterodimeric and heterotetrameric bi-, tri- and tetraspecific fusion proteins.

Description

[0001]Conditional agonists for receptors of the TNF receptor superfamily with a binding site for TRAF2 FIELD OF THE INVENTION The present invention relates to at least bispecific fusion protein constructs comprising a scaffold domain and binding domains of at least two specificities of which at least one is specific for a member of the tumor necrosis factor (TNF) receptor superfamily (TNFRSF) which contains a binding site for TNF receptor associated factor-2 (TRAF2). These constructs can be used to engage these TNFRSF receptors (TNFRs),for example to trigger the classical and / or alternative NFkappaB signaling pathways in the TNFR expressingcells. The invention also relates to an extendible protein library generated by coexpression of two amino acid chains from two supplemental groups of fusion proteins each composed of a constant scaffolding part and a binding domain enabling interaction with a cell surface- or extracellular matrix exposed protein / moleculeenabling the rapid and simple generation of heterodimeric and heterotetrameric bi-, tri- and tetraspecificfusion proteins. BACKGROUND Recombinant proteins / biologicals, especially antibodies, are the dominating category of drugs on the medical market and in clinical development. Beyond conventional antibodies and other naturally structured biologicals, there is growing relevance of genetically engineered biologicals with activities and functions not displayed by natural proteins, such as bi- or even trispecific antibodies or proteins. Typically, the multispecificity of recombinant proteins and antibodies and antibody fusion proteins is realized by Fab domain-containing antibody formats or linker connected protein domains. Due to the structurally modifications made in the constant antibody parts, IgG-based bispecific formats often have chain mis-pairing issues. Furthermore, the available formats for bi- and trispecific constructs have no or limited combinational capacity. Last not least, antibodies, antibody fusion proteins and fusion protein of non-antibody domains greatly vary with respect to productivity by state of the art methods in a poorly predicable way between 0 and good expression and this even between molecules of the same domain architecture. Accordingly, the preclinical development process of bi- and multispecific biologicals is largely “individualized” for each protein and thus rather elaborated and can only be transferred to a limited extent from one case to the next. Refs. 1-5 are general references exemplifying antibody-derived protein constructs known in the art. DESCRIPTION OF THE INVENTION The present invention is versatile and provides flexible, at least bispecific fusion protein constructs requiring no chain pairing mutations, which can be generated by combinational use of scaffold domains according to claim 1 i), e.g., constant antibody domain (CAD)-derivatives or irrelevant specificity antibody chains (ISACs, as reflected in claims 7 and 8). In particular, these constructs and the combinational approach enable the production of large cohorts of structurally equivalent and thus similarly processable of at least bispecific fusion protein constructs. These fusion protein constructs are based on the use of scaffold domains comprising the constant portion of an Fab fragment comprising (1) a CH1 domain and (2) a CL domain, e.g., constant domains or parts thereof of the two chains of an IgG molecule (Figure 1) or irrelevant-specificity light and heavy antibody chains (ISACs, as reflected in claims 7 and 8) or parts thereof (Figure 1). Furthermore, the fusion protein constructs comprise binding domains according to claim 1 ii) and claim 1 iii) encodable by a single-chain amino acid sequence that are genetically fused to the N-, C- or N- and C- terminus of the aforementioned scaffold domains (R1 to R4 in Figure 1). The present invention also relates to the design principles, methods, and use of expandable scaffold domain-based combinatorial library of fusion protein constructs for the rapid and simple generation of heterodimeric and heterotetrameric bi-, tri- and tetraspecific fusion proteins. The scaffold domain comprising the constant portion of an Fab fragment comprising (1) a CH1 domain and (2) a CL domain, e.g., comprising the light- and heavy chain derived constant antibody domains (CADs) or ISACs (as reflected in claims 7 and 8), are genetically fused with one or more binding domains according to claim 1 ii) and one or more binding domains according claim 1 iii). The one or more binding domains according to claim 1 ii) and one or more binding domains according claim 1 iii) can also be referred to as e.g., functional autarkic protein domains (FAPDs). The fusion protein constructs comprising the scaffold domains according to claim 1 i) or reflected in claims 7 or 8, and one or more domains according to claim 1 ii) and claim 1 iii) are freely combinable. By using small collections of fusion protein constructs according to the invention, the inventors obtained, by combinational complementary co-expression of the constructs according to the invention, a large library of bi- to tetraspecific heterodimeric and heterotetrameric fusion protein construct (e.g. CAD-FAPD fusion proteins, also referred to as CF fusion proteins). The one or more binding domains according to claim 1 ii) and claim 1 iii) (e.g., the FAPDs) can be of different molecular nature, e.g., VHHs (or 2x- 3xVHHs etc.), scFvs, ectodomains of membrane-bound proteins or soluble proteins and can be combined within a fusion protein construct according to the invention. Similarly, fusion protein constructs comprising a scaffold domain comprising or consisting of a full-length immunoglobulin (e.g., ISACs, reflected in claims 7 and 8) and one or more binding domains according to claim 1 ii) and claim 1 iii) covalently linked to at least one N-terminus and / or to at least one C-terminus of the scaffold domain (e.g., an N- and / or C- terminal FAPD) allow combinational complementary co-expression of a large library of bi- to tetraspecific heterodimeric or heterotetrameric fusion proteins (e.g., ISACs-FAPD fusion proteins, also referred to as IF fusion proteins). Based on the molecular nature of the one or more binding domains according to claim 1 ii) and claim 1 iii), distinct fusion protein types can be generated. The present invention also relates to a protein library comprising two or more different fusion protein constructs according to the present invention. The combination of two or more different fusion protein constructs according to the invention leads to heterodimeric or heterotetrameric fusion proteins. Due to the combinational nature of the protein library, its size grows exponentially with every novel domain added to the scaffold domain. The fusion protein constructs generated this way maintained the binding and functional properties of the one or more binding domains according to claim 1 ii) and claim 1 iii) or even displayed additional activities resulting from the cooperation of the one or more binding domains. For example, when VHH, 3xVHH and scFv domains specific for category II TNFRs are used, bi-, tri- and tetraspecific TNFR engagers with intrinsic and / or conditionally agonism can be generated dependent on the fusion protein domain architecture and the antigen / TNFR specificity of the one or more binding domains according to claim 1 ii) and claim 1 iii). Advantageously, the one or more binding domains according to claim 1 ii) directly bind to TNFRs interacting with TRAF2, resulting in both activation of the classical and alternative NFkappaB signaling pathway. It is self-understood that constant heavy chain antibody domains harboring point mutations modifying (e.g., reducing) FcgR-binding are also useful for the construction of fusion protein constructs according to the invention. Accordingly, the invention relates to the following preferred embodiments: 1. An at least bispecific fusion protein construct comprising:i) a scaffold domain comprising the constant portion of an Fab fragment comprising (1) a CH1domain and (2) a CLdomain, ii) one or more binding domains binding to a receptor selected from the group consisting ofTNFR2, CD40, 41BB, CD27, OX40, GITR, Fn14, CD30, BCMA and RANK, or a combination thereof, wherein the one or more binding domains are selected from the group consisting of a VHH, an scFv fragment, a ligand of said receptor, and a combination of two or more of a VHH, an scFv fragment, and a ligand of said receptor, and iii) one or more binding domains binding to a cell surface antigen or an extracellular matrixantigen which is different from the receptor bound by the one or more binding domains according to ii), wherein the binding domains according to ii) and iii) are covalently linked to at least one N- terminus and / or to at least one C-terminus of the scaffold domain according to i), and each binding domain according to ii) is covalently linked to a different N- or C-terminus of the scaffold domain according to i) than the one or more binding domains according to iii). 2. The fusion protein construct according to item 1, wherein the scaffold domain consists of theconstant portion of the Fab fragment consisting of (1) the CH1 domain, wherein the CH1 domain has preferably the amino acid sequence of SEQ ID NO: 35, and (2) the CLdomain, wherein the CLdomain has preferably the amino acid sequence of SEQ ID NO: 32. 3. The fusion protein construct according to item 1, wherein the scaffold domain comprises theconstant portion of an F(ab’)2fragment comprising two constant portions of Fab’ fragments, each of these portions comprising: (1) a CH1 domain followed by a hinge region and (2) a CLdomain. 4. The fusion protein construct according to item 3, wherein the scaffold domain consists of theconstant portion of the F(ab’)2fragment consisting of the two constant portions of Fab’ fragments, each of these portions consisting of: (1) the CH1 domain followed by the hinge region, wherein the CH1 domain followed by the hinge region has preferably the amino acid sequence of SEQ ID NO: 36, and (2) the CLdomain, wherein the CLdomain has preferably the amino acid sequence of SEQ ID NO: 32.The fusion protein construct according to item 1 or 3, wherein the scaffold domain comprises animmunoglobulin lacking the VHand VLregions.The fusion protein construct according to item 5, wherein the scaffold domain consists of animmunoglobulin lacking the VHand VLregions, and wherein the immunoglobulin lacking the VHand VLregions preferably consists of: a) an immunoglobulin heavy chain lacking the VHregion, wherein the immunoglobulin heavy chain lacking the VHregion preferably has the amino acid sequence of SEQ ID NO: 33 or 34, and b) a CLdomain, wherein the CLdomain preferably has the amino acid sequence of SEQ ID NO: 32.The fusion protein construct according to item 1, 3 or 5, wherein the scaffold domain comprisesa full-length immunoglobulin.The fusion protein construct according to item 7, wherein the scaffold domain consists of a full-length immunoglobulin.The fusion protein construct according to any one of the preceding items, comprising a series of2 or 3 binding domains according to ii) in a linear polypeptide chain, wherein the series is preferably a series of binding domains, preferably VHH domains, binding to the same receptor.The fusion protein construct according to any one of the preceding items, comprising a series of2 or 3 binding domains according to iii) in a linear polypeptide chain, wherein the series is preferably a series of binding domains, preferably VHH domains, binding to the same cell surface antigen or extracellular matrix antigen.The fusion protein construct according to any one of the preceding items, wherein said cellsurface antigen or extracellular matrix antigen is a cell surface antigen.The fusion protein construct according to any one of the preceding items, wherein said cellsurface antigen or extracellular matrix antigen is a protein.The fusion protein construct according to any one of the preceding items, wherein said cellsurface antigen or extracellular matrix antigen is a tumor antigen.The fusion protein construct according to any one of the preceding items, wherein said cellsurface antigen or extracellular matrix antigen is a human antigen.The fusion protein construct according to any one of the preceding items, wherein said cellsurface antigen is an antigen of an immune cell, optionally wherein the immune cell is a human immune cell, further optionally wherein the human immune cell is a human T lymphocyte.The fusion protein construct according to any one of the preceding items, wherein said cellsurface antigen or extracellular matrix antigen is selected from the group consisting of CD40, CD30, BCMA, B7-H3, CTLA4, EGFR, FAP, CXCR4, PDL1, PD1, PSMA, CD70, CD25, the high affinity and low affinity IL-2 receptor complex, CD38 and BAFF.The fusion protein construct according to any one of the preceding items, wherein said cellsurface antigen or extracellular matrix antigen is CD40 and the one or more binding domains according to ii) are selected from the group consisting of a binding domain binding to a receptor selected from TNFR2, 41BB, CD27, OX40, GITR, Fn14, CD30, BCMA and RANK, or a combination thereof.The fusion protein construct according to any one of the preceding items, wherein said cellsurface antigen or extracellular matrix antigen is CD30 and the one or more binding domains according to ii) are selected from the group consisting of a binding domain binding to a receptor selected from TNFR2, CD40, 41BB, CD27, OX40, GITR, Fn14, BCMA and RANK, or a combination thereof.The fusion protein construct according to any one of the preceding items, comprising one bindingdomain according to ii), wherein the binding domain according to ii) is a VHH.The fusion protein construct according to any one of items 1 to 18, comprising two bindingdomains according to ii) binding to the same receptor, wherein each of the two binding domains according to ii) are a VHH domain, or the two binding domains according to ii) are a series of 2 VHH domains in a linear polypeptide chain.The fusion protein construct according to any one of items 1 to 18, comprising two bindingdomains according to ii) binding to two different receptors selected from the group consisting of TNFR2, CD40, 41BB, CD27, OX40, GITR, Fn14, CD30, BCMA and RANK, and wherein each of the two binding domains are one VHH domain.The fusion protein construct according to any one of items 1 to 18, comprising three or fourbinding domains according to item 1 ii) binding to three or four different receptors selected from the group consisting of TNFR2, CD40, 41BB, CD27, OX40, GITR, Fn14, CD30, BCMA and RANK, and wherein each of the three or four binding domains are one VHH domain.The fusion protein construct according to any one of items 1 to 18, comprising three bindingdomains according to ii) binding to the same receptor, wherein each of the three binding domains according to ii) are a VHH domain, or the three binding domains according to ii) are a series of 3 VHH domains in a linear polypeptide chain.The fusion protein construct according to any one of items 1 to 18, comprising four bindingdomains according to ii) binding to the same receptor, and wherein each of the four binding domains according to ii) are a VHH domain, or the four binding domains according to ii) are a VHH domain and a series of 3 VHH domains in a linear polypeptide chain.The fusion protein construct according to any of the preceding items, wherein the scaffolddomain is from an IgG molecule, preferably from a human IgG1, IgG2, IgG3 or IgG4 molecule.The fusion protein construct of any one of items 5 to 25, wherein the full-length immunoglobulinof the scaffold domain or the immunoglobulin of the scaffold domain lacking the VHand VLregions contains a mutation modifying FcγR binding, preferably a mutation reducing FcγR binding.The fusion protein construct of any one of items 5 to 26, wherein the mutation is an N297Amutation.The fusion protein construct of any one of items 5 to 27, wherein the full-length immunoglobulinof the scaffold domain or the immunoglobulin lacking the VHand VLregions of the scaffold domain is a knob-into-hole immunoglobulin or contains a FC3C1 / FCkC mutation.The fusion protein construct according to any one of the preceding items, wherein the one ormore binding domains according to ii) are selected from one or more of the following: a0) an anti-41BB VHH; a1) an anti-41BB VHH having the amino acid sequence of SEQ ID NO: 1; a2) an anti-41BB VHH competing with the anti-41BB VHH of a1) for specific binding to 41BB;a3) an anti-41BB VHH having the same CDRs as the anti-41BB VHH of a1); anda4) an anti-41BB VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 1, at least 90% identical to the amino acid sequence of SEQ ID NO: 1, at least 95% identical to the amino acid sequence of SEQ ID NO: 1, at least 98% identical to the amino acid sequence of SEQ ID NO: 1, or at least 99% identical to the amino acid sequence of SEQ ID NO: 1 and preferably having the same CDRs as the anti-41BB VHH of a1); b1) an anti-41BB VHH having the amino acid sequence of SEQ ID NO: 2; b2) an anti-41BB VHH competing with the anti-41BB VHH of b1) for specific binding to 41BB;b3) an anti-41BB VHH having the same CDRs as the anti-41BB VHH of b1); andb4) an anti-41BB VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 2, at least 90% identical to the amino acid sequence of SEQ ID NO: 2, at least 95% identical to the amino acid sequence of SEQ ID NO: 2, at least 98% identical to the amino acid sequence of SEQ ID NO: 2, or at least 99% identical to the amino acid sequence of SEQ ID NO: 2 and preferably having the same CDRs as the anti-41BB VHH of b1); c1) an anti-41BB VHH having the amino acid sequence of SEQ ID NO: 3; c2) an anti-41BB VHH competing with the anti-41BB VHH of c1) for specific binding to 41BB;c3) an anti-41BB VHH having the same CDRs as the anti-41BB VHH of c1); andc4) an anti-41BB VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 3, at least 90% identical to the amino acid sequence of SEQ ID NO: 3, at least 95% identical to the amino acid sequence of SEQ ID NO: 3, at least 98% identical to the amino acid sequence of SEQ ID NO: 3, or at least 99% identical to the amino acid sequence of SEQ ID NO: 3 and preferably having the same CDRs as the anti-41BB VHH of c1); d0) an anti-CD40 VHH; d1) an anti-CD40 VHH having the amino acid sequence of SEQ ID NO: 5; d2) an anti-CD40 VHH competing with the anti-CD40 VHH of d1) for specific binding to CD40;d3) an anti-CD40 VHH having the same CDRs as the anti-CD40 VHH of d1); andd4) an anti-CD40 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 5, at least 90% identical to the amino acid sequence of SEQ ID NO: 5, at least 95% identical to the amino acid sequence of SEQ ID NO: 5, at least 98% identical to the amino acid sequence of SEQ ID NO: 5, or at least 99% identical to the amino acid sequence of SEQ ID NO: 5 and preferably having the same CDRs as the anti-CD40 VHH of d1); e1) an anti-CD40 VHH having the amino acid sequence of SEQ ID NO: 6; e2) an anti-CD40 VHH competing with the anti-CD40 VHH of e1) for specific binding to CD40;e3) an anti-CD40 VHH having the same CDRs as the anti-CD40 VHH of e1); ande4) an anti-CD40 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 6, at least 90% identical to the amino acid sequence of SEQ ID NO: 6, at least 95% identical to the amino acid sequence of SEQ ID NO: 6, at least 98% identical to the amino acid sequence of SEQ ID NO: 6, or at least 99% identical to the amino acid sequence of SEQ ID NO: 6 and preferably having the same CDRs as the anti-CD40 VHH of e1); f1) an anti-CD40 VHH having the amino acid sequence of SEQ ID NO: 7; f2) an anti-CD40 VHH competing with the anti-CD40 VHH of f1) for specific binding to CD40;f3) an anti-CD40 VHH having the same CDRs as the anti-CD40 VHH of f1); andf4) an anti-CD40 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 7, at least 90% identical to the amino acid sequence of SEQ ID NO: 7, at least 95% identical to the amino acid sequence of SEQ ID NO: 7, at least 98% identical to the amino acid sequence of SEQ ID NO: 7, or at least 99% identical to the amino acid sequence of SEQ ID NO: 7 and preferably having the same CDRs as the anti-CD40 VHH of f1); g0) a series of 2 anti-CD40 VHH domains in a linear polypeptide chain; g1) a series of 2 anti-CD40 VHH domains in a linear polypeptide chain, the linear polypeptide chain having the amino acid sequence of SEQ ID NO: 8; g2) an anti-CD40 VHH competing with the anti-CD40 VHH of g1) for specific binding to CD40;g3) an anti-CD40 VHH having the same CDRs as the anti-CD40 VHH of g1); andg4) an anti-CD40 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 8, at least 90% identical to the amino acid sequence of SEQ ID NO: 8, at least 95% identical to the amino acid sequence of SEQ ID NO: 8, at least 98% identical to the amino acid sequence of SEQ ID NO: 8, or at least 99% identical to the amino acid sequence of SEQ ID NO: 8 and preferably having the same CDRs as the anti-CD40 VHH of g1); h0) an anti-GITR VHH; h1) an anti-GITR VHH having the amino acid sequence of SEQ ID NO: 9; h2) an anti-GITR VHH competing with the anti-GITR VHH of h1) for specific binding to GITR;h3) an anti-GITR VHH having the same CDRs as the anti-GITR VHH of h1); andh4) an anti-GITR VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 9, at least 90% identical to the amino acid sequence of SEQ ID NO: 9, at least 95% identical to the amino acid sequence of SEQ ID NO: 9, at least 98% identical to the amino acid sequence of SEQ ID NO: 9, or at least 99% identical to the amino acid sequence of SEQ ID NO: 9 and preferably having the same CDRs as the anti-GITR VHH of h1); i0) an anti-OX40 VHH; i1) an anti-OX40 VHH having the amino acid sequence of SEQ ID NO: 10; i2) an anti-OX40 VHH competing with the anti-OX40 VHH of i1) for specific binding to OX40;i3) an anti-OX40 VHH having the same CDRs as the anti-OX40 VHH of i1); andi4) an anti-OX40 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 10, at least 90% identical to the amino acid sequence of SEQ ID NO: 10, at least 95% identical to the amino acid sequence of SEQ ID NO: 10, at least 98% identical to the amino acid sequence of SEQ ID NO: 10, or at least 99% identical to the amino acid sequence of SEQ ID NO: 10 and preferably having the same CDRs as the anti-OX40 VHH of i1); j0) an anti-41BB scFv; j1) an anti-41BB scFv having the amino acid sequence of SEQ ID NO: 21; j2) an anti-41BB scFv competing with the anti-41BB scFv of j1) for specific binding to 41BB;j3) an anti-41BB scFv having the same CDRs as the anti-41BB scFv of j1); andj4) an anti-41BB scFv having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 21, at least 90% identical to the amino acid sequence of SEQ ID NO: 21, at least 95% identical to the amino acid sequence of SEQ ID NO: 21, at least 98% identical to the amino acid sequence of SEQ ID NO: 21, or at least 99% identical to the amino acid sequence of SEQ ID NO: 21 and preferably having the same CDRs as the anti-41BB scFv of j1); k0) an anti-CD30 scFv; k1) an anti-CD30 scFv having the amino acid sequence of SEQ ID NO: 23; k2) an anti-CD30 scFv competing with the anti-CD30 scFv of k1) for specific binding to CD30;k3) an anti-CD30 scFv having the same CDRs as the anti-CD30 scFv of k1); andk4) an anti-CD30 scFv having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 23, at least 90% identical to the amino acid sequence of SEQ ID NO: 23, at least 95% identical to the amino acid sequence of SEQ ID NO: 23, at least 98% identical to the amino acid sequence of SEQ ID NO: 23, or at least 99% identical to the amino acid sequence of SEQ ID NO: 23 and preferably having the same CDRs as the anti-CD30 scFv of k1); l0) an anti-CD40 scFv; l1) an anti-CD40 scFv having the amino acid sequence of SEQ ID NO: 24; l2) an anti-CD40 scFv competing with the anti-CD40 scFv of l1) for specific binding to CD40;l3) an anti-CD40 scFv having the same CDRs as the anti-CD40 scFv of l1); andl4) an anti-CD40 scFv having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 24, at least 90% identical to the amino acid sequence of SEQ ID NO: 24, at least 95% identical to the amino acid sequence of SEQ ID NO: 24, at least 98% identical to the amino acid sequence of SEQ ID NO: 24, or at least 99% identical to the amino acid sequence of SEQ ID NO: 24 and preferably having the same CDRs as the anti-CD40 scFv of l1); m1) an anti-CD40 scFv having the amino acid sequence of SEQ ID NO: 25; m2) an anti-CD40 scFv competing with the anti-CD40 scFv of m1) for specific binding to CD40;m3) an anti-CD40 scFv having the same CDRs as the anti-CD40 scFv of m1); andm4) an anti-CD40 scFv having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 25, at least 90% identical to the amino acid sequence of SEQ ID NO: 25, at least 95% identical to the amino acid sequence of SEQ ID NO: 25, at least 98% identical to the amino acid sequence of SEQ ID NO: 25, or at least 99% identical to the amino acid sequence of SEQ ID NO: 25 and preferably having the same CDRs as the anti-CD40 scFv of m1); n0) an anti-TNFR2 VHH; n1) an anti-TNFR2 VHH having the amino acid sequence of SEQ ID NO: 29; n2) an anti-TNFR2 VHH competing with the anti-TNFR2 VHH of n1) for specific binding to TNFR2;n3) an anti-TNFR2 VHH having the same CDRs as the anti-TNFR2 VHH of n1); andn4) an anti-TNFR2 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 29, at least 90% identical to the amino acid sequence of SEQ ID NO: 29, at least 95% identical to the amino acid sequence of SEQ ID NO: 29, at least 98% identical to the amino acid sequence of SEQ ID NO: 29, or at least 99% identical to the amino acid sequence of SEQ ID NO: 29 and preferably having the same CDRs as the anti-TNFR2 VHH of n1); o1) an anti-TNFR2 VHH having the amino acid sequence of SEQ ID NO: 30; o2) an anti-TNFR2 VHH competing with the anti-TNFR2 VHH of o1) for specific binding to TNFR2;o3) an anti-TNFR2 VHH having the same CDRs as the anti-TNFR2 VHH of o1); ando4) an anti-TNFR2 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 30, at least 90% identical to the amino acid sequence of SEQ ID NO: 30, at least 95% identical to the amino acid sequence of SEQ ID NO: 30, at least 98% identical to the amino acid sequence of SEQ ID NO: 30, or at least 99% identical to the amino acid sequence of SEQ ID NO: 30 and preferably having the same CDRs as the anti-TNFR2 VHH of o1);p0) an anti-TNFR2 scFv;p1) an anti-TNFR2 scFv having the amino acid sequence of SEQ ID NO: 38; p2) an anti-TNFR2 scFv competing with the anti-TNFR2 scFv of p1) for specific binding to TNFR2;p3) an anti-TNFR2 scFv having the same CDRs as the anti-TNFR2 scFv of p1); andp4) an anti-TNFR2 scFv having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 38, at least 90% identical to the amino acid sequence of SEQ ID NO: 38, at least 95% identical to the amino acid sequence of SEQ ID NO: 38, at least 98% identical to the amino acid sequence of SEQ ID NO: 38, or at least 99% identical to the amino acid sequence of SEQ ID NO: 38 and preferably having the same CDRs as the anti-TNFR2 scFv of p1);q0) a series of 2 anti-TNFR2 VHH domains in a linear polypeptide chain;q1) a series of 2 anti-TNFR2 VHH domains in a linear polypeptide chain, the linear polypeptide chain having the amino acid sequence of SEQ ID NO: 40; q2) an anti-TNFR2 VHH competing with the anti-TNFR2 VHH of q1) for specific binding to TNFR2; q3) an anti-TNFR2 VHH having the same CDRs as the anti-TNFR2 VHH of q1); and q4) an anti-TNFR2 VHH having an amino acid sequence at least 85% identical to the amino acid sequence of SEQ ID NO: 40, at least 90% identical to the amino acid sequence of SEQ ID NO: 40, at least 95% identical to the amino acid sequence of SEQ ID NO: 40, at least 98% identical to the amino acid sequence of SEQ ID NO: 40, or at least 99% identical to the amino acid sequence of SEQ ID NO: 40 and preferably having the same CDRs as the anti-TNFR2 VHH of q1);r0) a series of 3 anti-TNFR2 VHH domains in a linear polypeptide chain;r1) a series of 3 anti-TNFR2 VHH domains in a linear polypeptide chain, the linear polypeptide chain having the amino acid sequence of SEQ ID NO: 41; r2) an anti-TNFR2 VHH competing with the anti-TNFR2 VHH of r1) for specific binding to TNFR2;r3) an anti-TNFR2 VHH having the same CDRs as the anti-TNFR2 VHH of r1); andr4) an anti-TNFR2 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 41, at least 90% identical to the amino acid sequence of SEQ ID NO: 41, at least 95% identical to the amino acid sequence of SEQ ID NO: 41, at least 98% identical to the amino acid sequence of SEQ ID NO: 41, or at least 99% identical to the amino acid sequence of SEQ ID NO: 41 and preferably having the same CDRs as the anti-TNFR2 VHH of r1); and s1) an anti-CD40 VHH having the amino acid sequence of SEQ ID NO: 42; s2) an anti-CD40 VHH competing with the anti-CD40 VHH of s1) for specific binding to CD40;s3) an anti-CD40 VHH having the same CDRs as the anti-CD40 VHH of s1); ands4) an anti-CD40 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 42, at least 90% identical to the amino acid sequence of SEQ ID NO: 42, at least 95% identical to the amino acid sequence of SEQ ID NO: 42, at least 98% identical to the amino acid sequence of SEQ ID NO: 42, or at least 99% identical to the amino acid sequence of SEQ ID NO: 42 and preferably having the same CDRs as the anti-CD40 VHH of s1).The fusion protein construct according to any one of the preceding items, wherein the one ormore binding domains according to iii) are selected from one or more of the following: aa0) an anti-BCMA VHH; aa1) an anti-BCMA VHH having the amino acid sequence of SEQ ID NO: 4; aa2) an anti-BCMA VHH competing with the anti-BCMA VHH of aa1) for specific binding to BCMA;aa3) an anti-BCMA VHH having the same CDRs as the anti-BCMA VHH of aa1); andaa4) an anti-BCMA VHH having an amino acid sequence at least 85% identical to the aminoacid sequence of SEQ ID NO: 4, at least 90% identical to the amino acid sequence of SEQ ID NO: 4, at least 95% identical to the amino acid sequence of SEQ ID NO: 4, at least 98% identical to the amino acid sequence of SEQ ID NO: 4, or at least 99% identical to the amino acid sequence of SEQ ID NO: 4 and preferably having the same CDRs as the anti-BCMA VHH of aa1); bb0) an anti-B7-H3 VHH; bb1) an anti-B7-H3 VHH having the amino acid sequence of SEQ ID NO: 11; bb2) an anti-B7-H3 VHH competing with the anti-B7-H3 VHH of bb1) for specific binding to B7- H3;bb3) an anti-B7-H3 VHH having the same CDRs as the anti-B7-H3 VHH of bb1); andbb4) an anti-B7-H3 VHH having an amino acid sequence at least 85% identical to the aminoacid sequence of SEQ ID NO: 11, at least 90% identical to the amino acid sequence of SEQ ID NO: 11, at least 95% identical to the amino acid sequence of SEQ ID NO: 11, at least 98% identical to the amino acid sequence of SEQ ID NO: 11, or at least 99% identical to the amino acid sequence of SEQ ID NO: 11 and preferably having the same CDRs as the anti-B7-H3 VHH of bb1); cc1) an anti-B7-H3 VHH having the amino acid sequence of SEQ ID NO: 12; cc2) an anti-B7-H3 VHH competing with the anti-B7-H3 VHH of cc1) for specific binding to B7- H3;cc3) an anti-B7-H3 VHH having the same CDRs as the anti-B7-H3 VHH of cc1); andcc4) an anti-B7-H3 VHH having an amino acid sequence at least 85% identical to the aminoacid sequence of SEQ ID NO: 12, at least 90% identical to the amino acid sequence of SEQ ID NO: 12, at least 95% identical to the amino acid sequence of SEQ ID NO: 12, at least 98% identical to the amino acid sequence of SEQ ID NO: 12, or at least 99% identical to the amino acid sequence of SEQ ID NO: 12 and preferably having the same CDRs as the anti-B7-H3 VHH of cc1); dd0) an anti-CTLA4 VHH; dd1) an anti-CTLA4 VHH having the amino acid sequence of SEQ ID NO: 13; dd2) an anti-CTLA4 VHH competing with the anti-CTLA4 VHH of dd1) for specific binding to CTLA4;dd3) an anti-CTLA4 VHH having the same CDRs as the anti-CTLA4 VHH of dd1); anddd4) an anti-CTLA4 VHH having an amino acid sequence at least 85% identical to the aminoacid sequence of SEQ ID NO: 13, at least 90% identical to the amino acid sequence of SEQ ID NO: 13, at least 95% identical to the amino acid sequence of SEQ ID NO: 13, at least 98% identical to the amino acid sequence of SEQ ID NO: 13, or at least 99% identical to the amino acid sequence of SEQ ID NO: 13 and preferably having the same CDRs as the anti-CTLA4 VHH of dd1); ee0) an anti-EGFR VHH; ee1) an anti-EGFR VHH having the amino acid sequence of SEQ ID NO: 14; ee2) an anti-EGFR VHH competing with the anti-EGFR VHH of ee1) for specific binding to EGFR;ee3) an anti-EGFR VHH having the same CDRs as the anti-EGFR VHH of ee1); andee4) an anti-EGFR VHH having an amino acid sequence at least 85% identical to the aminoacid sequence of SEQ ID NO: 14, at least 90% identical to the amino acid sequence of SEQ ID NO: 14, at least 95% identical to the amino acid sequence of SEQ ID NO: 14, at least 98% identical to the amino acid sequence of SEQ ID NO: 14, or at least 99% identical to the amino acid sequence of SEQ ID NO: 14 and preferably having the same CDRs as the anti-EGFR VHH of ee1); ff0) an anti-FAP VHH; ff1) an anti-FAP VHH having the amino acid sequence of SEQ ID NO: 15; ff2) an anti-FAP VHH competing with the anti-FAP VHH of ff1) for specific binding to FAP;ff3) an anti-FAP VHH having the same CDRs as the anti-FAP VHH of ff1); andff4) an anti-FAP VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 15, at least 90% identical to the amino acid sequence of SEQ ID NO: 15, at least 95% identical to the amino acid sequence of SEQ ID NO: 15, at least 98% identical to the amino acid sequence of SEQ ID NO: 15, or at least 99% identical to the amino acid sequence of SEQ ID NO: 15 and preferably having the same CDRs as the anti-FAP VHH of ff1); gg1) an anti-FAP VHH having the amino acid sequence of SEQ ID NO: 16; gg2) an anti-FAP VHH competing with the anti-FAP VHH of gg1) for specific binding to FAP;gg3) an anti-FAP VHH having the same CDRs as the anti-FAP VHH of gg1); andgg4) an anti-FAP VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 16, at least 90% identical to the amino acid sequence of SEQ ID NO: 16, at least 95% identical to the amino acid sequence of SEQ ID NO: 16, at least 98% identical to the amino acid sequence of SEQ ID NO: 16, or at least 99% identical to the amino acid sequence of SEQ ID NO: 16 and preferably having the same CDRs as the anti-FAP VHH of gg1); hh0) an anti-CXCR4 VHH; hh1) an anti-CXCR4 VHH having the amino acid sequence of SEQ ID NO: 17; hh2) an anti-CXCR4 VHH competing with the anti-CXCR4 VHH of hh1) for specific binding to CXCR4;hh3) an anti-CXCR4 VHH having the same CDRs as the anti-CXCR4 VHH of hh1); andhh4) an anti-CXCR4 VHH having an amino acid sequence at least 85% identical to the aminoacid sequence of SEQ ID NO: 17, at least 90% identical to the amino acid sequence of SEQ ID NO: 17, at least 95% identical to the amino acid sequence of SEQ ID NO: 17, at least 98% identical to the amino acid sequence of SEQ ID NO: 17, or at least 99% identical to the amino acid sequence of SEQ ID NO: 17 and preferably having the same CDRs as the anti-CXCR4 VHH of hh1); ii0) an anti-PDL1 VHH; ii1) an anti-PDL1 VHH having the amino acid sequence of SEQ ID NO: 18; ii2) an anti-PDL1 VHH competing with the anti-PDL1 VHH of ii1) for specific binding to PDL1;ii3) an anti-PDL1 VHH having the same CDRs as the anti-PDL1 VHH of ii1); andii4) an anti-PDL1 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 18, at least 90% identical to the amino acid sequence of SEQ ID NO: 18, at least 95% identical to the amino acid sequence of SEQ ID NO: 18, at least 98% identical to the amino acid sequence of SEQ ID NO: 18, or at least 99% identical to the amino acid sequence of SEQ ID NO: 18 and preferably having the same CDRs as the anti-PDL1 VHH of ii1); jj1) an anti-PD1 VHH having the amino acid sequence of SEQ ID NO: 19; jj2) an anti-PD1 VHH competing with the anti-PD1 VHH of jj1) for specific binding to PD1;jj3) an anti-PD1 VHH having the same CDRs as the anti-PD1 VHH of jj1); andjj4) an anti-PD1 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 19, at least 90% identical to the amino acid sequence of SEQ ID NO: 19, at least 95% identical to the amino acid sequence of SEQ ID NO: 19, at least 98% identical to the amino acid sequence of SEQ ID NO: 19, or at least 99% identical to the amino acid sequence of SEQ ID NO: 19 and preferably having the same CDRs as the anti-PD1 VHH of jj1); kk0) an anti-PSMA VHH; kk1) an anti-PSMA VHH having the amino acid sequence of SEQ ID NO: 20; kk2) an anti-PSMA VHH competing with the anti-PSMA VHH of kk1) for specific binding to PSMA;kk3) an anti-PSMA VHH having the same CDRs as the anti-PSMA VHH of kk1); andkk4) an anti-PSMA VHH having an amino acid sequence at least 85% identical to the aminoacid sequence of SEQ ID NO: 20, at least 90% identical to the amino acid sequence of SEQ ID NO: 20, at least 95% identical to the amino acid sequence of SEQ ID NO: 20, at least 98% identical to the amino acid sequence of SEQ ID NO: 20, or at least 99% identical to the amino acid sequence of SEQ ID NO: 20 and preferably having the same CDRs as the anti-PSMA VHH of kk1); ii0) an anti-BCMA scFv; ll1) an anti-BCMA scFv having the amino acid sequence of SEQ ID NO: 22; ll2) an anti-BCMA scFv competing with the anti-BCMA scFv of ll1) for specific binding to BCMA;ll3) an anti-BCMA scFv having the same CDRs as the anti-BCMA scFv of ll1); andll4) an anti-BCMA scFv having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 22, at least 90% identical to the amino acid sequence of SEQ ID NO: 22, at least 95% identical to the amino acid sequence of SEQ ID NO: 22, at least 98% identical to the amino acid sequence of SEQ ID NO: 22, or at least 99% identical to the amino acid sequence of SEQ ID NO: 22 and preferably having the same CDRs as the anti-BCMA scFv of ll1); mm0) an anti-CD70 scFv; mm1) an anti-CD70 scFv having the amino acid sequence of SEQ ID NO: 26; mm2) an anti-CD70 scFv competing with the anti-CD70 scFv of mm1) for specific binding to CD70;mm3) an anti-CD70 scFv having the same CDRs as the anti-CD70 scFv of mm1); andmm4) an anti-CD70 scFv having an amino acid sequence at least 85% identical to the aminoacid sequence of SEQ ID NO: 26, at least 90% identical to the amino acid sequence of SEQ ID NO: 26, at least 95% identical to the amino acid sequence of SEQ ID NO: 26, at least 98% identical to the amino acid sequence of SEQ ID NO: 26, or at least 99% identical to the amino acid sequence of SEQ ID NO: 26 and preferably having the same CDRs as the anti-CD70 scFv of mm1); nn1) an anti-CD70 scFv having the amino acid sequence of SEQ ID NO: 27; nn2) an anti-CD70 scFv competing with the anti-CD70 scFv of nn1) for specific binding to CD70;nn3) an anti-CD70 scFv having the same CDRs as the anti-CD70 scFv of nn1); andnn4) an anti-CD70 scFv having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 27, at least 90% identical to the amino acid sequence of SEQ ID NO: 27, at least 95% identical to the amino acid sequence of SEQ ID NO: 27, at least 98% identical to the amino acid sequence of SEQ ID NO: 27, or at least 99% identical to the amino acid sequence of SEQ ID NO: 27 and preferably having the same CDRs as the anti-CD70 scFv of nn1); oo1) a Baff receptor-binding scBaff (single-chain Baff) comprising three protomers of Baff connected by peptide linkers, wherein the scBaff (single-chain Baff) is identical to the amino acid sequence of SEQ ID NO: 28 or has an amino acid sequence at least 85% identical to the amino acid sequence of SEQ ID NO: 28, at least 90% identical to the amino acid sequence of SEQ ID NO: 28, at least 95% identical to the amino acid sequence of SEQ ID NO: 28, at least 98% identical to the amino acid sequence of SEQ ID NO: 28, or at least 99% identical to the amino acid sequence of SEQ ID NO: 28; pp1) a TNFR2-binding scTNF80 (single-chain TNF80) comprising three protomers of TNF80, a mutant of TNF with two mutations preventing binding to TNFR1 thus ensuring specific TNFR2 binding, connected by peptide linkers, wherein the scTNF80 (single-chain TNF80) is identical to the amino acid sequence of SEQ ID NO: 37 or has an amino acid sequence at least 85% identical to the amino acid sequence of SEQ ID NO: 37, at least 90% identical to the amino acid sequence of SEQ ID NO: 37, at least 95% identical to the amino acid sequence of SEQ ID NO: 37, at least 98% identical to the amino acid sequence of SEQ ID NO: 37, or at least 99% identical to the amino acid sequence of SEQ ID NO: 37;qq0) an anti-CD38 VHH;qq1) an anti-CD38 VHH having the amino acid sequence of SEQ ID NO: 43; qq2) an anti-CD38 VHH competing with the anti-CD38 VHH of qq1) for specific binding to CD38;qq3) an anti-CD38 VHH having the same CDRs as the anti-CD38 VHH of qq1); andqq4) an anti-CD38 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 43, at least 90% identical to the amino acid sequence of SEQ ID NO: 43, at least 95% identical to the amino acid sequence of SEQ ID NO: 43, at least 98% identical to the amino acid sequence of SEQ ID NO: 43, or at least 99% identical to the amino acid sequence of SEQ ID NO: 43 and preferably having the same CDRs as the anti-CD38 VHH of qq1);rr1) an anti-CD38 VHH having the amino acid sequence of SEQ ID NO: 44; rr2) an anti-CD38 VHH competing with the anti-CD38 VHH of rr1) for specific binding to CD38;rr3) an anti-CD38 VHH having the same CDRs as the anti-CD38 VHH of rr1); andrr4) an anti-CD38 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 44, at least 90% identical to the amino acid sequence of SEQ ID NO: 44, at least 95% identical to the amino acid sequence of SEQ ID NO: 44, at least 98% identical to the amino acid sequence of SEQ ID NO: 44, or at least 99% identical to the amino acid sequence of SEQ ID NO: 44 and preferably having the same CDRs as the anti-CD38 VHH of rr1);ss0) an anti-CD25 VHH;ss1) an anti-CD25 VHH which does not block IL-2 binding;ss2) an anti-CD25 VHH blocking IL-2 binding;ss3) an anti-CD25 VHH having the amino acid sequence of SEQ ID NO: 45; ss4) an anti-CD25 VHH competing with the anti-CD25 VHH of ss3) for specific binding to CD25;ss5) an anti-CD25 VHH having the same CDRs as the anti-CD25 VHH of ss3); andss6) an anti-CD25 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 45, at least 90% identical to the amino acid sequence of SEQ ID NO: 45, at least 95% identical to the amino acid sequence of SEQ ID NO: 45, at least 98% identical to the amino acid sequence of SEQ ID NO: 45, or at least 99% identical to the amino acid sequence of SEQ ID NO: 45 and preferably having the same CDRs as the anti-CD25 VHH of ss3); tt1) an anti-CD25 VHH having the amino acid sequence of SEQ ID NO: 46; tt2) an anti-CD25 VHH competing with the anti-CD25 VHH of tt1) for specific binding to CD25;tt3) an anti-CD25 VHH having the same CDRs as the anti-CD25 VHH of tt1); andtt4) an anti-CD25 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 46, at least 90% identical to the amino acid sequence of SEQ ID NO: 46, at least 95% identical to the amino acid sequence of SEQ ID NO: 46, at least 98% identical to the amino acid sequence of SEQ ID NO: 46, or at least 99% identical to the amino acid sequence of SEQ ID NO: 46 and preferably having the same CDRs as the anti-CD25 VHH of tt1);uu0) an anti-CD30 VHH;uu1) an anti-CD30 VHH having the amino acid sequence of SEQ ID NO: 48; uu2) an anti-CD30 VHH competing with the anti-CD30 VHH of uu1) for specific binding to CD30;uu3) an anti-CD30 VHH having the same CDRs as the anti-CD30 VHH of uu1); anduu4) an anti-CD30 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 48, at least 90% identical to the amino acid sequence of SEQ ID NO: 48, at least 95% identical to the amino acid sequence of SEQ ID NO: 48, at least 98% identical to the amino acid sequence of SEQ ID NO: 48, or at least 99% identical to the amino acid sequence of SEQ ID NO: 48 and preferably having the same CDRs as the anti-CD30 VHH of uu1); vv1) IL2; vv2) an IL2 mutant; and vv3) an IL2 having the amino acid sequence of SEQ ID NO: 47; and ww1) any one or more of the domains as defined in item 29, or any one or more of the domains according to d0), d1), d2), d3, d4), e1), e2), e3), e4), f1), f2), f3), f4), g0), g1), g2), g3), g4), k0), k1), k2), k3), k4), l0), l1), l2), l3), l4), m1), m2), m3), m4), s1), s2), s3), or s4) as defined in item 29.The fusion protein construct according to any one of the preceding items, wherein the fusionprotein construct does not comprise more than two scFv fragments.The fusion protein construct according to any one of the preceding items, wherein the fusionprotein construct does not comprise more than one scFv fragment.The fusion protein construct according to any one of the preceding items, wherein the fusionprotein construct does not comprise any scFv fragment.The fusion protein construct according to any one of the preceding items, wherein each of theN-termini of the scaffold domain according to i) is linked to one or more binding domains according to ii) or one or more binding domains according to iii).The fusion protein construct according to any one of the preceding items, wherein all of the oneor more binding domains according to ii) and all of the one or more binding domains according to iii) are VHH domains.A pharmaceutical composition comprising a fusion protein construct according to any one of thepreceding items.A protein library comprising two or more different fusion protein constructs according to any oneof items 1-35.The protein library according to item 37, the library comprising ten or more different fusion proteinconstructs according to any one of items 1-35.A nucleic acid, or a set of nucleic acids, encoding the fusion protein construct according to anyone of items 1-35.A set of nucleic acids, encoding the protein library according to item 37 or 38.A recombinant cell containing a nucleic acid, or a set of nucleic acids, according to item 39 andexpressing the fusion protein construct of any one of items 1-35.A method for producing a fusion protein construct according to any one of items 1-35, the methodcomprising expressing the nucleic acid or set of nucleic acids according to item 39 in a recombinant cell according to item 41, and harvesting the fusion protein construct.43. A method for producing a protein library according to item 37 or 38, the method comprisingexpressing the set of nucleic acids according to item 40 together or separately in cells, and obtaining the protein library. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1: Domain architecture of scaffold domains, e.g., constant antibody domain (CAD) scaffolds (e.g. CH1-CH3 plus CL; CH1-hinge plus CL; CH1 plus CL) and irrelevant-specificity antibody chain (ISAC) scaffolds (as reflected in claims 7 and 8), and positioning possibilities for one or more binding domains (also named as functional autarkic protein domains (FAPDs) according to ii) and iii) of claim 1) useful to generate conditional agonists of receptors of the TNF receptor superfamily with a binding site for TRAF2 individually or large scale as a library. Upper panel: First scheme: Domain architecture of IgG1 with a N297A point mutation. N297A indicate a mutation preventing / reducing FcgR-binding. Second scheme: heterotetrameric scaffold domain according to i) of claim 1, e.g., a constant antibody domain (CAD) scaffold, derived from IgG1(N297A) comprising all constant parts of this molecule. Third and fourth scheme: a heterotetrameric and a heterodimeric constant antibody domain (CAD) scaffold domain according to i) of claim 1 obtained by deletion of the Fc domain or Fc domain plus hinge region from the full constant antibody part of an IgG. R1 to R4 indicate the N- and C- termini of the scaffold allowing genetic fusion of protein domains / peptide sequences, especially binding domains according to ii) and iii) of claim 1, e.g., functional autarkic protein domains (FAPDs). Scaffold domains according to i) of claim 1 of IgG1 wt, other IgG1 mutants and other IgG subclass variants are of equivalent architecture. Lower panel: scaffold domains as reflected in claims 7 and 8, e.g., irrelevant-specificity antibody chains (ISACs) scaffold, derived from IgG1(N297A). Scaffold domains as reflected in claims 7 and 8 obtained by deletion of the Fc domain or Fc domain plus hinge region. R1 to R4 indicate the N- and C-termini of the scaffold allowing genetic fusion of protein domains / peptide sequences, especially binding domains according to ii) and iii) of claim 1, e.g., functional autarkic protein domains (FAPDs). Scaffold domains as reflected in claims 7 and 8 of IgG1 wild-type, other IgG1 mutants and other IgG subclass variants are of equivalent architecture. The scaffold domains as reflected in claims 7 and 8 and shown in the first and second scheme enable production of heterodimeric tetramers and the scaffold domains as reflected in claims 7 and 8 and shown in the third scheme can serve as the basis for the production of heterodimeric proteins. Figure 2: Combinational use of FAPD-fused chains of heterodimer-forming CADs to generate libraries (=large collections) of bi-, tri-, etc. specific FAPD-CAD fusion proteins A variety of structurally defined heterodimeric fusion proteins with a Fab1-derived CAD can be generated in a combinational manner by co-expression of a CL domain, genetically fused on the R1 and / or R3 position with one or more binding domains according to ii) and iii) of claim 1, e.g. a VHH domain, scFv domain or another monomeric protein domain derived of a ligand or receptor protein, and a CH1 domain, genetically fused on the R2 and / or R4 with one or more binding domains according to ii) and iii) of claim 1, e.g. a VHH domain, scFv domain or another monomeric protein domain derived of a ligand or receptor protein. Figure 3: Mono- and bivalent VHH:CD40 fusion proteins with a single PDL1-specific anchoring domain show PDL1-restricted agonism. HT1080-CD40 cells were challenged with Empty vector (EV) or PDL1-transfected HEK293 cells along with the indicated concentrations of mono- (left panel) and bivalent (right panel) VHH:CD40 fusion proteins with the constant antibody domains (CAD) of a Fab domain harboring a PDL1-specific VHH domain on position 3, thus on the C-terminus of the CL-containing peptide chain. Next day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for CD40 activation. Please note: Both constructs display any activity in cocultures with EV cells but both trigger a strong response in the presence of PDL1-expressing cells. Figure 4: A bivalent VHH:CD40 fusion proteins with a single FAP-specific anchoring domain showFAP-restricted agonism. HT1080-CD40 cells were challenged with murine B16 cells or stable transfectantsof B16 expressing the fibroblast activation protein FAP and increasing concentrations of bivalent VHH:CD40 fusion proteins with the constant antibody domains (CAD) of a Fab domain harboring a FAP-specific VHH domain on position 3. Next day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for CD40 activation. Upper panel: A variety of structurally defined types of CAD-FAPD (CD) fusion proteins can be generated in a combinatorial manner by co-expression of light and heavy chains of CADs (LC CAD, HC CAD) genetically fused on the R1 (LC CAD) and R2 (HC CAD) position with a FAPD domain, e.g. a VHH domain, scFv domain or another monomeric protein domain derived of a ligand or receptor protein, and the R3 (LC CAD) and R4 (HC CAD) position without further domain or fused with a FAPD domain. Figure 5: Monovalent CD40 fusion proteins with three or four TNFR2 targeting VHH-domains display TNFR2-dependent CD40 agonism and to a varying extend constitutive TNFR2 agonism. Left and middle panel: The indicated 1:1 mixtures of HT1080-muCD40, HT1080-TNFR2 and HT1080 cells were stimulated with increasing concentrations of the indicated constructs. Next day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for muCD40 and / or TNFR2 activation. Note 1: murine CD40 (muCD40) is able to IL8 production in muCD40-transfected human cells. Note 2: In the absence of CD40, the tri- and even better the tetravalency for TNFR2 is sufficient to trigger TNFR2 activity. Note 3: When both, TNFR2 and CD40, are present there is synergistic IL8 production arguing for conditional TNFR2-dependent CD40 activation. This is explicitly demonstrated in the right panel. Right panel: The indicated 1:1 mixtures of HT1080-muCD40 and HEK293 cells transfected with empty vector or expressing a fusion protein of the extracellular domain of TNFR2 (TNFR2ed) with an GPI-anchor were stimulated with increasing concentrations of the indicated constructs. Next day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for muCD40 activation. Figure 6: Combinational use of FAPD-fused chains of heterotetramer-forming CADs to generate libraries (=large collections) of bi-, tri-, etc. specific FAPD-CAD fusion proteins. A variety of structurally defined heterotetrameric fusion proteins with an IgG1(N297A)-derived CAD can be generated in a combinational manner by co-expression of a CL domain, genetically fused on the R1 and / or R3 with one or more binding domains according to ii) and iii) of claim 1, e.g. a VHH domain, scFv domain or another monomeric protein domain derived of a ligand or receptor protein, and a CH1-CH2-CH3 domain, genetically fused on the R2 and / or R4 with one or more binding domains according to ii) and iii) of claim 1, e.g. a VHH domain, scFv domain or another monomeric protein domain derived of a ligand or receptor protein. Figure 7: Domain architecture of fusion proteins comprising a scaffold domain according to i) of claim 1, e.g., constant antibody domain (CAD) of IgG1(N297A), with CD40- and PDL1-specific nanobodies (Nbs) as binding domains / FAPDs according to ii) and iii) of claim 1 investigated infigures 8 and 9. Please note, a VHHs with irrelevant specificity, VHH(dummy) or VHH:irr., were partlyincluded to cover potential VHH domain effects not related to the binding specificity of the VHHs. The constructs differ with respect to the number (2 or 4) and positioning (N- and C-terminal) of the CD40- and PDL-specific binding domains resulting in 26 examples which represent construct types with different positioning of the TNF receptor binding domain (TRBD) and other binding domains. Figure 8: CD40xPDL1 bispecific Nb-fusion proteins with two VHH:CD40 domains and two or four additional PDL1-specific Nb domains display PDL1-dependent CD40 activation. HT1080-CD40 cells were co-cultivated with HEK293 cells either transiently transfected with empty vector (EV) or PDL1. Next day, cells were stimulated with the indicated fusion proteins containing CD40- and or PDL1-specific VHH domains. Some constructs also contained VHH domains with irrelevant specificity (= dummy VHH = VHH:irr.). After an additional day, cell culture supernatants were analyzed for their IL8 content by ELISA. IL8 production is indicative for CD40 activation. TRBD positioning types 1-14 have N-terminal CD40-VHHs, 15 – 18 C-terminal ones. VHH:PDL1 served as anchoring domain (AD) for the binding of the plasma membrane anchoring target (AT) PDL1. Figure 9: Inactive / poorly agonistic tetravalent CD40 Nb-fusion proteins with two or four PDL1-specific Nbs display PDL1-dependent enhanced CD40 activation. HT1080-CD40 cells were co-cultivated with HEK293 cells either transiently transfected with empty vector (EV) or PDL1. Next day, cells were stimulated with the indicated fusion proteins. After an additional day, cell culture supernatants were analyzed for their IL8 content by ELISA. IL8 production is indicative for CD40 activation. TRBD positioning types 19-22 have four N-terminal CD40-VHHs, TRBD positioning type 23-26 have two N- and two- C-terminal CD40-VHHs. VHH:PDL1 served as anchoring domain (AD) for the binding of the plasma membrane anchoring target (AT) PDL1. Figure 10: Bivalent VHH:CD40 fusion proteins with two additional VHHs, specific for cell surface antigens, as anchoring domains (ADs) show anchoring-dependent CD40 agonism irrespective of the AD specificity. HT1080-CD40 cells, which produce high levels of IL8 in response to CD40 stimulation, were co-cultivated with HEK293 cells transiently transfected with empty vector (EV) or the antigen recognized by the VHH AD. Next day, cell cocultures were stimulated with the indicated fusion proteins. After an additional day, cell culture supernatants were analyzed for their IL8 content by ELISA as readout for CD40 activation. Figure 11: Bivalent VHH:CD40 fusion proteins with two additional VHHs, specific for cell surface antigens, as anchoring domains (ADs) show anchoring-dependent CD40 agonism irrespective of the AD specificity. HT1080-CD40 cells were either co-cultivated with HT1080-FAP cells stably transfected with the anchoring target (AT) FAP or LNCaP, Jurkat and A431 cells with endogenous expression of the ATs PSMA, CXCR4 and EGFR co-cultivated. HEK293 cells serves as AT negative control cells. Next day, cell cocultures were stimulated with the indicated fusion proteins and finally cell culture supernatants were analyzed for their IL8 content by ELISA. Figure 12: Bivalent VHH:CD40 fusion proteins with two scFvs, specific for cell surface antigens, as anchoring domains (ADs) show anchoring-dependent CD40 agonism irrespective of the scFv specificity. HT1080-CD40 cells were co-cultivated with HEK293 cells transiently transfected with empty vector (EV) or the antigen recognized by the scFv AD. Next day, cell cocultures were stimulated with the indicated fusion proteins containing CD40- and or AT-specific scFv ADs. Figure 13: CD40xPDL1 bispecific bivalent CD40 Nb- fusion proteins with two PDL1-specific Nbs and CD40-specific Nbs distinct from the VHH:CD40(V12t) display PDL1-dependent CD40 activation. HT1080-CD40 cells were co-cultivated with HEK293 cells transiently transfected with empty vector (EV) or PDL1. Next day, cell cocultures were stimulated with the indicated fusion proteins containing the CD40- specific VHHs 1B6 or 1E10. After an additional day, cell culture supernatants were analyzed for their IL8 content by ELISA. Figure 14: Bivalent scFv:CD40 fusion proteins with VHH anchoring domains (VHH-ADs) show cell surface antigen-mediated anchoring-dependent CD40 agonism. HT1080-CD40 cells were co-cultivated with HEK293 cells transiently transfected with empty vector (EV) or the antigen recognized by the VHH-AD. Alternatively, HT1080-CD40 cells were co-cultivated with LNCaP cells expressing endogenously PMSA or HEK293 cells. Next day, cell cocultures were stimulated with the indicated fusion proteins containing CD40-specific scFvs and AT-specific VHHs. After an additional day, cell culture supernatants were analyzed for their IL8 content by ELISA. Figure 15: Tetravalent VHH:CD40 fusion proteins with VHH anchoring domains (Ads) show enhanced CD40 agonism if cell surface antigen / target-binding is possible. HT1080-CD40 cells were co-cultivated with HEK293 cells transiently transfected with empty vector (EV) or the antigen / protein recognized by the AD, thus PDL1 (left panel), BCMA (middle panel) and PD1 (right panel). Next day, cell cocultures were stimulated with the indicated fusion proteins and after an additional day, cell culture supernatants were analyzed for their IL8 content by ELISA. Figure 16: Tetravalent VHH:CD40 fusion proteins with a scFv or cytokine anchoring domain show enhanced CD40 agonism if cell surface antigen / receptor-binding is possible. HT1080-CD40 cells were co-cultivated with CD70 expressing CHO cells or as negative control CHO cells or were co-cultivated with HEK293 cells transiently transfected with empty vector (EV) or BaffR-GPI. Next day, cell cocultures were stimulated with the indicated fusion proteins and after an additional day, cell culture supernatants were analyzed by ELISA for their IL8, which is indicative for CD40 activation. Figure 17: Tetravalent 2xVHH:CD40 fusion proteins with two additional VHH anchoring domains (ADs) show enhanced CD40 agonism if cell surface antigen / target-binding is possible. LNCaP and Jurkat cells expressing the anchoring targets (ATs) PSMA and CXCR4 or HEK293 cells lacking PMSA and CXCR4 expression were co-cultured. Alternatively, HT1080-CD40 cells were co-cultivated with HEK293 cells transiently transfected with empty vector (EV) or PDL1 and PD1. Next day, cell cocultures were stimulated with the indicated fusion proteins containing 2xVHH:CD40 as effector domain and or AT- specific ADs. After an additional day, cell culture supernatants were analyzed for their IL8 content by ELISA. Figure 18: Bivalent VHH:41BB fusion proteins with two additional VHH ADs show enhanced 41BB agonism if cell surface antigen / target-binding is possible. HT1080-41BB cells, which robustly produce IL8 in response to 41BB stimulation, were co-cultivated with HEK293 cells transiently transfected with empty vector (EV) or PDL1 or BCMA-GPI encoding expression plasmids. Next day, cell cocultures were stimulated with the indicated fusion proteins containing either the 41BB-specific VHH A-Ye-19 or the 41BB-specific VHH Yr13 and targeting BCMA and PDL1. After an additional day, cell culture supernatants were analyzed for their IL8 content by ELISA indicative for 41BB activation. Figure 19: VHH:OX40 fusion proteins with VHH ADs show enhanced OX40 agonism if cell surface antigen / target-binding is possible. HT1080-OX40 cells, which produce IL8 in response to OX40 stimulation, were co-cultivated with HEK293 cells transiently transfected with empty vector (EV) or PDL1. Next day, cocultures were stimulated with the indicated fusion protein containing an OX40-specific VHH and CTLA4- and PDL1-specific VHHs as AT- specific ADs. After an additional day, cell culture supernatants were analyzed for their IL8 content by ELISA. Figure 20: Trispecific VHH:OX40 or VHH:41BB fusion proteins with additional VHH ADs of two distinct specificities show enhanced OX40 and 41BB agonism if one of the two AT-specific cell surface antigens is present. HT1080-41BB cells (upper panel) or HT1080-OX40 cells (lower panel) were co-cultivated with HEK293 cells transiently transfected with empty vector (EV) or PDL1 or BCMA-GPI. Next day, cocultures were stimulated with the indicated fusion protein and after an additional day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for 41BB and OX40 activation. Figure 21. A bivalent VHH:GITR fusion protein with two additional CXCR4-specific VHHs as AD show CXCR4-dependent GITR agonism. HT1080-GITR cells, which robustly produce IL8 in response to GITR stimulation, were co-cultivated with HEK293 cells or Jurkat cells endogenously expressing CXCR4. After an additional day, cell culture supernatants were analyzed for their IL8 content by ELISA. Figure 22. Bivalent scFv:41BB fusion proteins with VHH anchoring domains show cell surface antigen-mediated AT-dependent 41BB agonism. HT1080-41BB cells were co-cultivated with HEK293 cells transiently transfected with empty vector (EV) or expression plasmids encoding PDL1 or the GPI-anchored extracellular domains of CD40 and BCMA, thus variants of these receptors not able to signal. Next day, cell cocultures were stimulated with the indicated fusion proteins and after an additional day, cell culture supernatants were analyzed for their IL8 content by ELISA. Figure 23. Hexavalent trispecific VHH:CD40 fusion proteins with a VHH:CD40 domain N-terminally fused to the CL chain and addressing two different ATs show enhanced CD40 agonism if one of the two AD-specific cell surface antigens is present. HT1080-CD40 cells were co-cultivated with the indicated AT-positive and -negative cell variants. Next day, cocultures were stimulated with increasing concentrations of the various fusion proteins and after an additional day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for CD40 activation. Note I: OX40 and BCMA were used here as ATs. OX40 and BCMA similar to CD40 belong to the TNFRSF and can potentially induce IL8 production. To avoid that OX40 and BCMA signaling contribute to IL8 production in testing CD40 agonism, deletion mutants comprising only the extracellular domain (ed) of OX40 with a GPI anchor was used. Note II: The expression level of the AT determines / restricts the maximal amount of molecules that can acquire AT-dependent CD40 agonism. Thus, different maximal CD40 responses do not necessarily reflect different intrinsic capabilities of the ADs to empower the VHH:CD40 domains of the constructs to act as agonists but rather different AT expression levels. Figure 24. Hexavalent trispecific VHH:CD40 fusion proteins with a VHH:CD40 domain C-terminally fused to the CL chain and addressing two different ATs show enhanced CD40 agonism if one of the two AD-specific cell surface antigens is present. HT1080-CD40 cells were co-cultivated with the indicated AT-positive and -negative cell variants. Next day, cocultures were stimulated with increasing concentrations of the various fusion proteins and after an additional day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for CD40 activation. Note I: OX40 and BCMA were used here as ATs. OX40 and BCMA similar to CD40 belong to the TNFRSF and can potentially induce IL8 production. To avoid that OX40 and BCMA signaling contribute to IL8 production in testing CD40 agonism, deletion mutants comprising only the extracellular domain of OX40 with a GPI anchor was used. Note II: The expression level of the AT determines / restricts the maximal amount of molecules that can acquire AT-dependent CD40 agonism. Thus, different maximal CD40 responses do not necessarily reflect different intrinsic capabilities of the ADs to empower the VHH:CD40 domains of the constructs to act as agonists but rather different AT expression levels. Figure 25. Octavalent trispecific VHH:CD40 fusion proteins with a VHH:CD40 domain N-terminally fused to the CL and CH1-CH3 chain and addressing two different ATs show basal CD40 agonism which is enhanced if one of the two AD-specific cell surface antigens is present. HT1080-CD40 cells were co-cultivated with the indicated AT-positive and -negative cell variants. Next day, cocultures were stimulated with increasing concentrations of the various fusion proteins and after an additional day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for CD40 activation. Note I: 41BB and BCMA were used here as ATs.41BB and BCMA similar to CD40 belong to the TNFRSF and can potentially induce IL8 production. To avoid that OX40 and BCMA signaling contribute to IL8 production in testing CD40 agonism, deletion mutants comprising only the extracellular domain (ed) of OX40 with a GPI anchor was used. Note II: The expression level of the AT determines / restricts the maximal amount of molecules that can acquire AT-dependent CD40 agonism. Thus, different maximal CD40 responses do not necessarily reflect different intrinsic capabilities of the ADs to empower the VHH:CD40 domains of the constructs to act as agonists but rather different AT expression levels. Figure 26. Octavalent trispecific VHH:CD40-VHH:OX40-VHH:AT fusion proteins show CD40 and OX40agonism when two of the three binding possibilities are realized. HT1080-CD40 cells or HT1080-OX40cells were co-cultivated with cell variants positive for the expression of the ATs (293-BCMA(ed), 293- OX40(ed), 293-PDL, BJAB (endogenous CD40) and lacking AT expression (293-EV). Next day, cocultures were stimulated with increasing concentrations of the various fusion proteins and after an additional day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for CD40 activation. Note I: To be able to verify whether OX40 binding results in enhanced CD40 activation and vice versa that CD40 binding result in enhanced OX40 activation, in the cocultures with IL8-responsive HT1080-CD40 cells (left panels), a signaling deficient OX40 deletion mutant only comprising the extracellular domain and a GPI anchor was used as AT and in the cocultures with IL8-responsive HT1080-OX40 cells (right panels), BJAB cells, which endogenously express CD40 but do not produce relevant IL8 in response to CD40 triggering were used as AT. BCMA were used here again as AT in a signaling defective variant. Note II: HT1080-CD40 and HT1080- OX40 cells reach different maximal IL8 levels in response to activation of CD40 and OX40. Note III: As the constructs contain 4 VHH:CD40 domains there were again basal CD40 agonism. Figure 27. An octavalent trispecific VHH:CD40-VHH:41BB-VHH:PDL1 fusion protein show CD40 and41BB agonism when two of the three binding possibilities are realized. HT1080-CD40 cells or HT1080-41BB cells were co-cultivated as indicated with HEK293 cells transfected with empty vector (EV) or PDL1- or 41BB(ed)-encoding constructs or were co-cultivated with BJAB cells having endogenous CD40 expression but do not produce IL8 in response to stimulation of the latter. Next day, cocultures were stimulated with increasing concentrations of the protein and after an additional day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for CD40 and 41BB activation. Note I: HT1080-CD40 and HT1080- 41BB cells reach quite different maximal IL8 levels in response to activation of CD40 and 41BB. Note II: As the constructs contain 4 VHH:CD40 domains there were again basal CD40 agonism. Figure 28. Octavalent trispecific VHH:CD40 fusion proteins with a VHH:CD40 domain N-terminally fused to the CL and CH1-CH3 chain and addressing two different ATs by VHH- and non-antibody ligand-based binding domains according to ii) and iii) of claim 1 show basal CD40 agonism which is enhanced if one of the AD-specific cell surface targets is present. HT1080-CD40 cells were co-cultivated with the indicated AT-positive and -negative cell variants and stimulated with increasing concentrations of the various fusion proteins. Next day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for CD40 activation. Note I: The TNFRSF receptors BaffR, 41BB and OX40 BCMA were used here as ATs. Since these receptors can potentially induce IL8 production, signaling defective deletion mutants comprising the extracellular domain (rd) plus an GPI anchor were used. Note II: The FAPD scBaff (single- chain Baff) is composed of three protomers of the ligand Baff connected by peptide linkers and bind three receptor molecules. Besides BaffR, Baff / scBaff also binds TACI and BCMA. The latter two ATs have not tested here. Figure 29. Hexavalent trispecific VHH:CD40 fusion proteins with a VHH:CD40 domain N-terminally fused to the CL and addressing two different ATs by VHH- and scFvs FAPDs show conditional CD40 agonism when one of the AD-specific cell surface targets is present. HT1080-CD40 cells were co- cultivated with the indicated AT-positive and -negative cell variants and stimulated with increasing concentrations of the various fusion proteins. Next day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for CD40 activation. Figure 30. Hexavalent trispecific VHH:CD40 fusion proteins with a VHH:CD40 domain N-terminally fused to the CH1-CH3 and addressing two different ATs by VHH- and scFvs binding domains according to ii) and iii) of claim 1 show conditional CD40 agonism when one of the AD-specific cell surface targets is present. HT1080-CD40 cells were co-cultivated with the indicated AT-positive and - negative cell variants and stimulated with increasing concentrations of the various fusion proteins. Next day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for CD40 activation. Note I: BJAB cells also express CD40 but do not produce IL8. HT1080-CD40 cells are thus the cellular source of IL8 production.Figure 31. VHH-(CL / CH1-CH3) fusion proteins show superior productivity. Conventional IgG1antibodies with and without the N297A mutation and IgG1 fusion proteins with a scFv domain fused to the heavy chain C-terminus as well as VHH-fusion proteins of the type indicated were generated by transient transfection of HEK293 cells with 1:1 mixtures of the expression constructs encoding the LC and HC of an IgG1 antibody or pairs of interest of VHH-CL and VHH-(CH1-CH3) chains using the PEI method. All chains contained an internal Flag tagged. Supernatants were collected after 5-7 days and analyzed by WB using anti-Flag antibodies. Concentrations of recombinant proteins were estimated by comparison with Flag-tagged standard proteins. Antibodies analyzed cover > 50 antibodies and > 40 antigen specificities. VHHs used in the VHH-(CL / CH1-CH3) cover > 40 nanobodies with > 20 specificities (not all used in the patent). “V” indicates fusion of a nanobody domain, “3V” indicate fusion of a triple nanobody cassette and “0” indicates no fusion to positions R1 to R4 according to figure 1. Figure 32. A bivalent VHH:TNFR2 CAD fusion protein with two additional VHHs, specific for cell surface antigen / immune checkpoint molecule PD1, as anchoring domain (ADs) show anchoring-dependent TNFR2 agonism. HT1080-TNFR2 cells, which produce high levels of IL8 in response to TNFR2stimulation, were challenged with Jurkat cells not expressing PD1 or Jurkat transfectants with PD1 expression. Cell cocultures were stimulated with the indicated fusion protein and the next day, cell culture supernatants were analyzed for their IL8 content by ELISA as readout for TNFR2 activation. Figure 33. Octavalent trispecific VHH:CD40 CAD fusion proteins with a VHH:CD40 domain N- terminally fused to the CL and CH1-CH3 chain and addressing two different ATs show basal CD40 agonism which is enhanced if one of the two AD-specific cell surface antigens is present. HT1080- CD40 cells were challenged with HEK293 cells transfected with EV or expression plasmids encoding TNFR2ed-GPI and / or 41BBed-GPI along with increasing concentrations of VHH:CD40(V12t)- VHH:CD40(V1t)-IgG1(N297A)-VHH:41BB-VHH:TNFR2(C188). Next day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for CD40 activation. Note I: 41BB and TNFR2 were used here as ATs.41BB and TNFR2 similar to CD40 belong to the TNFRSF and can potentially induce IL8 production. To avoid that 41BB and TNFR2 signaling contribute to IL8 production in testing CD40 agonism, deletion mutants of these receptors comprising only the extracellular domain (ed) with a GPI anchor were used. Figure 34. Tetravalent bispecific VHH CAD fusion proteins with addressing two different TNFR types display reciprocal conditional dual agonism. Cocultures of the indicated HT1080 cells and HT1080-TNFR transfectants were challenged with increasing concentrations of the indicated fusion proteins Next day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for activation of GITR, CD40 and TNFR2. Figure 35. Tetravalent bispecific VHH-scFv CAD fusion proteins with addressing two different TNFR types display reciprocal conditional dual agonism. Cocultures of the indicated HT1080 cells and HT1080- TNFR transfectants were challenged with increasing concentrations of the indicated fusion proteins. Next day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for activation of 41BB, CD40 and TNFR2. Figure 36. Hexavalent trispecific VHH CAD fusion proteins addressing three distinct types of TNFRs display reciprocal conditional agonism. Cocultures of the indicated HT1080 cells and HT1080-TNFR transfectants were challenged with increasing concentrations of the indicated fusion proteins. Next day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for activation of GITR, 41BB, CD40 and TNFR2. Figure 37. Bivalent VHH:CD40 fusion proteins with two additional VHHs, specific for cell surface antigens, as anchoring domains (ADs) show anchoring-dependent CD40 agonism irrespective of the AD specificity (i.e., irrespective of the concrete nature and properties of the AT recognized by the AD). HT1080-CD40 cells were cocultivated with the indicated anchoring target (AT)-positive and -negative cell variants. Next day, cocultures were stimulated with increasing concentrations of the various fusion proteins and after an additional day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for CD40 activation. Note I: The expression level of the AT determines / restricts the maximal amount of molecules that can acquire AT-dependent CD40 agonism. Thus, different maximal CD40 responses do not necessarily reflect different intrinsic capabilities of the ADs to empower the VHH:CD40 domains of the constructs to act agonistically but rather different AT expression levels. Figure 38. Bivalent VHH:TNFR2 fusion proteins with two additional VHHs, specific for cell surface antigens, as anchoring domains (ADs) show anchoring-dependent TNFR2 agonism irrespective of the AD specificity (i.e., irrespective of the concrete nature and properties of the AT recognized by the AD). HT1080-TNFR2 cells were cocultivated with the indicated AT-positive and -negative cell variants. Next day, cocultures were stimulated with increasing concentrations of the various fusion proteins and after an additional day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for TNFR2 activation. Figure 39. Tetravalent bispecific VHH:TNFR2-VHH:CD40 CAD fusion proteins show dual reciprocalconditional agonism. HT1080-CD40 cells or HT1080-TNFR2 cells were cocultivated with the indicatedtransfectants. Next day, cocultures were stimulated with increasing concentrations of the various fusion proteins and after an additional day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for CD40 activation. Note I: To be able to verify whether TNFR2 binding results in enhanced CD40 activation and vice versa that CD40 binding results in enhanced TNFR2 activation, in the cocultures with IL8- responsive HT1080-CD40 cells, HEK293 transient transfectants expressing a signaling deficient TNFR2 deletion mutant only comprising the extracellular domain and a GPI anchor (TNFR2-GPI) was used as AT- expressing cells and in the cocultures with IL8-responsive HT1080-TNFR2 cells, HEK293 cells, which transiently express a signaling deficient CD40 deletion mutant only comprising the extracellular domain and a GPI anchor (CD40-GPI), were used as AT-expressing cells in the cocultures with IL8-responsive HT1080- TNFR2 cells.HEK293 cells transfected with emty vector (EV) served as AT-negative control cells. Figure 40. Trispecific VHH:CD40 fusion proteins with additional VHH ADs of two distinct specificitiesshow enhanced CD40 agonism if one of the two anchoring targets (ATs) is present. HT1080-CD40cells were co-cultivated with HEK293 cells transiently transfected with empty vector (EV) or CD25 or PD1. Next day, cocultures were stimulated with the indicated fusion protein and after an additional day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for CD40 activation. Please note, the two constructs contains different CD25-specific nanobody domains (G01 and A02, blocking and non-blocking IL-2 binding) indicating that the epitope recognized in CD25 is not important for the CD25-dependent activation of CD40. Figure 41. Trispecific VHH:CD40-VHH:TNFR2 fusion proteins with an additional cytokine (IL2) AD show enhanced CD40 or TNFR2 agonism if the AT-specific cell surface antigen (IL2 receptor) or the other receptor is present as AT. HT1080-CD40 or HT1080-TNFR2 cells were co-cultivated with HEK293 cells transiently transfected with empty vector (EV) or expression constructs encoding CD25 (= IL2 receptor alpha-chain) or the GPI-anchoring fusion proteins of the extracellular domains of CD40 and TNFR2. Next day, cocultures were stimulated with the indicated fusion protein and after an additional day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for CD40 or TNFR2 activation. Note I: To be able to verify whether TNFR2 binding results in enhanced CD40 activation and vice versa that CD40 binding results in enhanced TNFR2 activation, in the cocultures with IL8-responsive HT1080-CD40 cells, the signaling deficient TNFR2 deletion mutant only comprising the extracellular domain and a GPI anchor was used as AT and in the cocultures with IL8-responsive HT1080-TNFR2 cells, HEK293 cells, which transiently express a signaling deficient CD40 deletion mutant only comprising the extracellular domain and a GPI anchor were used in the cocultures with IL8-responsive HT1080-TNFR2 cells. Figure 42. Trispecific VHH:CD40-VHH:TNFR2 fusion proteins with an additional VHH anchoring domain (VHH-AD) display dual reciprocal conditional TNFR2 / CD40 agonism and anchoring target(AT)-dependent conditional CD40- and TNFR2 agonism. HT1080-CD40 or HT1080-TNFR2 cells wereco-cultivated with HEK293 cells transiently transfected with empty vector (EV) or expression vectors encoding PDL1 or fusion proteins of the extracellular domains of CD40 or TNFR2 with a GPI-anchoring sequence (CD40-GPI and TNFR2-GPI, respectively). Next day, cocultures were stimulated with the indicated fusion protein and after an additional day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for CD40 or TNFR2 activation. Note I: To be able to verify whether TNFR2 binding results in enhanced CD40 activation and vice versa that CD40 binding results in enhanced TNFR2 activation, in the cocultures with IL8-responsive HT1080-CD40 cells, HEK293 transfectants expressing a signaling deficient TNFR2 deletion mutant only comprising the extracellular domain and a GPI anchor (TNFR2-GPI) was used as AT-expressing cells. In the cocultures with IL8-responsive HT1080-TNFR2 cells, HEK293 cells, which transiently express a signaling deficient CD40 deletion mutant only comprising the extracellular domain and a GPI anchor (CD40-GPI), were used as AT-expressing cells. Figure 43. Trispecific VHH:CD40 fusion proteins with a cytokine (IL2) and a nanobody (VHH:FAP(3C4) as ADs elicit CD40 agonism if one of the cell surface molecules (CD25 or FAP) recognized by the ADs is present. HT1080-CD40 cells were co-cultivated with HEK293 cells transiently transfected with empty vector (EV) or CD25 (= IL2 receptor alpha-chain) respectively with B16 cells and B16 cells stably transfected with FAP. Next day, cocultures were stimulated with the indicated fusion protein and after an additional day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for CD40 activation. Figure 44. Trispecific VHH:CD40 fusion proteins with VHH ADs of two distinct specificities show enhanced CD40 agonism if one of the two AT-specific cell surface antigens is present. HT1080-CD40 cells were co-cultivated with HEK293 cells transiently transfected with empty vector (EV) or BCMA or PD1 or HT1080-CD40 cells were co-cultivated with Jurkat cells endogenously expressing CXCR4 or LNCAP cells endogenously expressing PSMA. Then, cocultures were stimulated with the indicated fusion protein and after an additional day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for CD40 activation. HEK293 empty vector transfected cells served as AT-negative cells in all cases. Figure 45. Tetraspecific VHH:CD40 fusion proteins with VHH ADs of three distinct specificities show enhanced CD40 agonism if one of the three AT-specific cell surface antigens is present. HT1080- CD40 cells were co-cultivated with HEK293 cells transiently transfected with empty vector (EV) or BCMA or PD1 or HT1080-CD40 cells were co-cultivated with Jurkat cells endogenously expressing CXCR4 or B16 cells stably transfected with FAP. Then, cocultures were stimulated with the indicated fusion protein and after an additional day, cell culture supernatants were analyzed by ELISA for their IL8 content indicative for CD40 activation. HEK293 empty vector transfected cells and B16 cells served as AT-negative cells. Figure 46. Tetravalent VHH:CD40 fusion proteins with two or four VHH anchoring domains (ADs)show enhanced CD40 agonism if cell surface antigen / target-binding is possible. LNCAP and Jurkatcells expressing the anchoring targets (ATs) PSMA and CXCR4 or HEK293 cells transiently transfected with BCMA or stably transfected B16-FAP or corresponding controls were co-cultivated with HT1080-CD40. Then, cell cocultures were stimulated with the indicated fusion proteins containing tetravalent VHH:CD40 as effector domain. After an additional day, cell culture supernatants were analyzed for their IL8 content by ELISA. DETAILED DESCRIPTION OF THE INVENTION Definitions and General Techniques Unless otherwise defined below, the terms used in the present invention shall be understood in accordance with their common meaning known to the person skilled in the art. All publications, patents and patent applications cited herein are hereby incorporated by reference in their entirety for all purposes. Publications referred to herein may be cited by specifying the full literature reference in the text, or by naming the author and the publication year (e.g., “Wajant et al. 2003”) or a reference number and by specifying the corresponding full literature reference in the “references” section. All proteins in accordance with the invention, including the fusion protein constructs of the invention, can be obtained by methods known in the art. Such methods include methods for the production of recombinant proteins. The fusion protein constructs of the invention can be expressed in recombinant host cells according to the invention. Recombinant host cells of the invention are preferably mammalian cells such as HEK cells, CHO cells or COS cells. It will be understood that the fusion protein constructs of the invention are meant to optionally include a secretion signal peptide sequence. Similarly, the fusion protein constructs of the invention are meant to also optionally include affinity tags, e.g., in order to facilitate purification, and optional protease cleavage sites between the tag and the fusion protein construct, e.g., in order to facilitate removal of the tags by protease cleavage. Likewise, it will be understood that the fusion protein constructs of the invention are meant to optionally include the respective pro-peptides. It is also understood that any reference to amino acid sequences referred to herein is meant to encompass not only the unmodified amino acid sequence but also typical posttranslational modifications of these amino acid sequences (e.g., glycosylation or deamidation of amino acids, the clipping of particular amino acids or other posttranslational modifications) occurring in cellular expression systems known in the art, including mammalian cells such as HEK or PancO2 cells. The terms “antibody” or “immunoglobulin” used herein refer to any functional antibody that is capable of specific binding to the antigen of interest, as generally outlined in chapter 7 of Paul, W.E. (Ed.).: Fundamental Immunology 2nd Ed. Raven Press, Ltd., New York 1989, which is incorporated herein by reference. Without particular limitation, the terms “antibody” or “immunoglobulin” encompass antibodies from any appropriate source species, including chicken and mammalian such as mouse, goat, non-human primate and human. Preferably, the antibody is a humanized or human antibody. The antibody is preferably a monoclonal antibody which can be prepared by methods well-known in the art. The term “antibody” encompasses an IgG-1, -2, - 3, or -4, IgE, IgA, IgM, or IgD isotype antibody. The term “antibody” encompasses monomeric antibodies (such as IgD, IgE, IgG) or oligomeric antibodies (such as IgA or IgM). The terms “antibody” or “immunoglobulin” also encompass – without particular limitations - isolated antibodies and modified antibodies such as genetically engineered antibodies, e.g., chimeric, humanized or human antibodies. For example, the terms “IgG1”, “IgG2”, “IgG3” or “IgG4” as used in accordance with the invention encompass chimeric, humanized and human IgG1, IgG2, IgG3 and IgG4, respectively. As used herein, an “IgG” can be a naturally occurring IgG or a mutated IgG, as is known in the art. The term IgG comprises any of IgG1, IgG2, IgG3, and IgG4. The nomenclature of the antibodies, antibody fragments and mutations thereof follow the terms as known in the art. It will be understood by a person skilled in the art that in accordance with the invention, this known nomenclature is to be applied also to the fusion protein constructs of the invention. For example, the known nomenclature is to be applied also to an antibody which forms part of a fusion protein construct of the invention.Each monomer of an antibody comprises two heavy chains and two light chains, as generally known in theart. Of these, each light chain consists of one variable domain (VL) and one constant domain (CL). Eachheavy chain has one variable domain (VH) and three or four constant domains (CH1, CH2, CH3, CH4). The heavy and light chain variable domains comprise (in an N-terminal to C-terminal order) the regions FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4 (FR, framework region; CDR, complementarity determining region which is also known as hypervariable region). The identification and assignment of the above-mentioned antibody regions within the antibody sequence is generally in accordance with Kabat et al. (Sequences of proteins of immunological interest, U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, Bethesda, Md.1983), or Chothia et al. (Conformations of immunoglobulin hypervariable regions. Nature.1989 Dec 21-28;342(6252):877-83.), or may be performed by using the IMGT / V-QUEST software described in Giudicelli et al. (IMGT / V-QUEST, an integrated software program for immunoglobulin and T cell receptor V-J and V-D-J rearrangement analysis. Nucleic Acids Res.2004 Jul 1;32(Web Server issue):W435-40.), which is incorporated herein by reference. Preferably, the antibody regions indicated above are identified and assigned by using the IMGT / V-QUEST software. A “monoclonal antibody” is an antibody from an essentially homogenous population of antibodies, wherein the antibodies are substantially identical in sequence (i.e., identical except for minor fraction of antibodies containing naturally occurring sequence modifications such as amino acid modifications at their N- and C- termini). Unlike polyclonal antibodies which contain a mixture of different antibodies directed to either a single epitope or to numerous different epitopes, monoclonal antibodies are directed to the same epitope and are therefore highly specific. The term “monoclonal antibody” includes (but is not limited to) antibodies which are obtained from a monoclonal cell population derived from a single cell clone, as for instance the antibodies generated by the hybridoma method described in Köhler and Milstein (Nature, 1975 Aug 7;256(5517):495- 7) or Harlow and Lane (“Antibodies: A Laboratory Manual” Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York 1988). A monoclonal antibody may also be obtained from other suitable methods, including phage display techniques such as those described in Clackson et al. (Nature.1991 Aug 15;352(6336):624- 8) or Marks et al. (J Mol Biol.1991 Dec 5;222(3):581-97). A monoclonal antibody may be an antibody that has been optimized for antigen-binding properties such as decreased Kd values, optimized association and dissociation kinetics by methods known in the art. For instance, Kd values may be optimized by display methods including phage display, resulting in affinity-matured monoclonal antibodies. The term “monoclonal antibody” is not limited to antibody sequences from particular species of origin or from one single species of origin. Thus, the meaning of the term “monoclonal antibody” encompasses chimeric monoclonal antibodies such as humanized monoclonal antibodies and human antibodies. According to the invention, the fusion protein construct is “at least bispecific”, i.e., it can bind at least to two different targets, i.e., a receptor as referred to herein in connection with domain ii), and an antigen as defined in connection with domain iii). According to the invention, the generated fusion proteins may, for instance, be bi-, tri, tetraspecific, i.e., it can bind at least to two, three, or four different targets. “Humanized antibodies” are antibodies which contain human sequences and a minor portion of non-human sequences which confer binding specificity to an antigen of interest. Typically, humanized antibodies are generated by replacing hypervariable region sequences from a human acceptor antibody by hypervariable region sequences from a non-human donor antibody (e.g., a mouse, rabbit, rat donor antibody) that binds to an antigen of interest. In some cases, framework region sequences of the acceptor antibody may also be replaced by the corresponding sequences of the donor antibody. In addition to the sequences derived from the donor and acceptor antibodies, a “humanized antibody” may either contain other (additional or substitute) residues or sequences or not. Such other residues or sequences may serve to further improve antibody properties such as binding properties (e.g., to decrease Kd values) and / or immunogenic properties (e.g., to decrease antigenicity in humans). Non-limiting examples for methods to generate humanized antibodies are known in the art, e.g., from Riechmann et al. (Nature.1988 Mar 24; 332(6162):323-7) or Jones et al. (Nature. 1986 May 29-Jun 4; 321(6069):522-5). The term “human antibody” relates to an antibody containing human variable and constant domain sequences. This definition encompasses antibodies having human sequences bearing single amino acid substitutions or modifications which may serve to further improve antibody properties such as binding properties (e.g., to decrease Kd values) and / or immunogenic properties (e.g., to decrease antigenicity in humans). The term “human antibody” excludes humanized antibodies where a portion of non-human sequences confers binding specificity to an antigen of interest. A “binding domain” as used herein refers to a domain capable of binding to a surface protein structure, e.g., a receptor. This capability can, for instance, be determined by determining the capability of the binding domain to compete with an antibody for specific binding to the molecular structure, e.g., the receptor by methods known in the art. The binding portion may contain one or more fragments of the antibody, e.g., a VHH, an scFv fragment, a ligand of said receptor, and a combination of a VHH, an scFv fragment, and / or a ligand of said surface protein, e.g., receptor. Without particular limitation, the binding domain can be produced by any suitable method known in the art, including recombinant DNA methods and preparation of VHH, scFv fragments, ligands of said receptor. A binding domain encoded by a single DNA sequence / having a single amino acid chain is a “functional autarkic protein domain (FAPD)” as referred to herein. The term “Fab fragment” or fragment antigen-binding region (Fab region) refers to a region on an antibody that binds to antigens. It is composed of one constant and one variable domain of each of the heavy and the light chain. The variable domain contains the paratope (the antigen-binding site), comprising a set of complementarity-determining regions, at the amino terminal end of the monomer. The term “F(ab’)2 fragment” is well known in the art. An F(ab’)2 fragment, also known as an F(ab’)2 antibody, contain two antigen-binding regions, e.g., comprises two Fab fragments, joined at the hinge through disulfide bridges or alternatively by adhesive domains. In contrast to full length antibodies, such as immunoglobulin G, F(ab’)2 fragments lack large parts of the Fc fragment. The term “hinge region” is well-known in the art. The hinge region is a stretch of heavy chains between the Fab and Fc portions. Its unique structure and position provide segmental flexibility, which is essential for normal functioning of antibodies (e.g., for crosslinking two antigens or binding two antigenic determinants on the same antigen molecule). The term “Fab' fragment” is well known in the art. Fab’ fragments can be formed by the reduction of F(ab')2 fragments. The Fab' fragment contains a free sulfhydryl group that may be alkylated or utilized in conjugation with an enzyme, toxin or other protein of interest. Fab' is derived from F(ab')2; therefore, it may contain a small portion of Fc. The term “VHH” is to be understood in accordance with its known meaning in the art. VHH are oftentimes also referred to as “nanobodies”. VHH can, for instance, be engineered from heavy-chain antibodies such as those found in camelids. VHH engineered from heavy-chain antibodies are oftentimes referred to as “single- domain antibody (sdAb)”. Thus, in one preferred embodiment, one, more, or all occurrences of a “VHH” in connection with the invention can optionally be replaced by “single-domain antibody (sdAb)”. The term “scFv” (single chain variable fragment) is well known in the art. A scFv fragment is generally understood to consist of the variable domain of the heavy and light chains of a monoclonal antibody. The Fv fragment is the smallest fragment produced from IgG and IgM that contains a complete antigen-binding site. Fv fragments have the same binding properties and similar three-dimensional binding characteristics as Fab. The VH and VL chains of the Fv fragments are held together by non-covalent interactions. The term “Fc fragment” is well-known in the art. A Fc fragment is generally understood to contain the CH2 and CH3 region and part of the hinge region linked together by one or more disulfides and noncovalent interactions. Fc fragments are generally produced from fragmentation of an IgG molecule. Fc fragments are generated entirely from the heavy chain constant region of an immunoglobulin. The Fc fragment cannot bind antigen, but it is responsible for the effector functions of antibodies, such as complement fixation. An “fusion protein construct” according to the invention comprises a scaffold domain comprising the constant portion of an Fab fragment comprising (1) a CH1 domain and (2) a CLdomain, i) one or more binding domains binding to a receptor selected from the group consisting ofTNFR2, CD40, 41BB, CD27, OX40, GITR, Fn14, CD30, BCMA and RANK, or a combination thereof, wherein the one or more binding domains are selected from the group consisting of a VHH, an scFv fragment, a ligand of said receptor, and a combination of two or more of a VHH, an scFv fragment, and a ligand of said receptor, and ii) one or more binding domains binding to a cell surface antigen or an extracellular matrixantigen which is different from the receptor bound by the one or more binding domains according to ii), wherein the binding domains according to ii) and iii) are covalently linked to at least one N-terminus and / or to at least one C-terminus of the scaffold domain according to i), and each binding domain according to ii) is covalently linked to a different N- or C-terminus of the scaffold domain according to i) than the one or more binding domains according to iii). In connection with the invention, domain(s) according to iii) are also referred to as “anchoring domains” or “AD”. It is understood that a fusion protein construct according to the invention is typically a protein wherein two or more polypeptide chains are linked together. They can be linked together covalently, e.g., by covalent linkages. Such covalent linkages may be one or more disulfide linkages. Alternatively, the covalent linkages may be obtained by chemical conjugation (preferably by chemical conjugation using click chemistry), and / or they may be any other covalent linkage which is known in the art as a suitable link for proteins. Alternatively, a fusion protein construct according to the invention may be a protein wherein two or more polypeptide chains are linked together non-covalently (e.g., by non-covalent interactions). The fusion protein construct according to the invention may be a fusion protein construct which is derivatized or linked to a different molecule. For example, molecules that may be linked to the fusion protein construct are a molecular label (e.g., a fluorescent, luminescent, colored, or radioactive molecule) and / or a pharmaceutical agent. Generally, in connection with the fusion protein constructs of the invention, it will be understood that the parts (e.g., domains) of the fusion protein constructs may be fused using linker sequences. In that case, the fusion protein construct of the invention will comprise such linker sequences. Suitable linker sequences are known in the art and comprise, for example, peptide linkers, without being limited thereto. The term “covalently linked to” is meant to encompass direct and indirect covalent linkages. For instance, in accordance with the phrase “wherein the binding domains according to ii) and iii) are covalently linked to at least one N-terminus and / or to at least one C-terminus of the scaffold domain according to i), and each binding domain according to ii) is covalently linked to a different N- or C-terminus of the scaffold domain according to i) than the one or more binding domains according to iii)” the respective binding domains can be covalently linked to the at least one N-terminus and / or to the at least one C-terminus of the scaffold domain according to i) directly or indirectly. For example, if a series of binding domains according to ii) is covalently linked to an N-terminus or C-terminus of the scaffold domain according to i), the first binding domain of the series may be covalently linked to the N-terminus or C-terminus directly (or indirectly by using a linker), whereas the second and possible further binding domain(s) of the series will be covalently linked to the N- terminus or C-terminus indirectly. Where the fusion protein constructs are constructs wherein “each of the N-termini of the scaffold domain according to i) is linked to one or more binding domains according to ii) or one or more binding domains according to iii)”, this means that each N-terminus of the scaffold domain according to i) is linked to one or more of the indicated domains, i.e., that there are no free N-termini of the scaffold domain according to i). For example, in such a fusion protein construct, some N-termini may be linked to one or more binding domains according to ii), and the remaining N-termini may be linked one or more binding domains according to iii), such that there are no free N-termini of the scaffold domain according to i). As used herein, the term “mutation reducing FcγR binding” in connection with the Fc domain of an IgG of the fusion protein constructs of the invention encompasses any mutation that reduces binding of the fusion protein construct to at least one of the Fc gamma receptors as compared to a corresponding reference fusion protein construct where the mutation is absent from the Fc domain. Whether a mutation reduces FcγR binding to an Fc gamma receptor can be determined by methods known in the art such as comparative surface plasmon resonance measurements of the binding of the fusion protein construct and the reference fusion protein construct to the respective immobilized recombinant Fc gamma receptor. Mutations reducing FcγR binding are well known in the art. For IgG1 such as chimeric, humanized or human IgG1, known mutations reducing FcγR binding include, but are not limited to: N297A, N297D, N297Q, N297G, E233P, L234A, L234F, L235A, L235E, P331S,P329A, P329G, P331S, P238S, LALA (LALA = mutation of Leucine 234 to Alanine and Leucine 235 to Alanine), A330S, G237A, M252Y, S254T, S228P, T256E, M252F, M252S, M252W, M252T, T256S, T256R, T256Q, T256D, H268A, and combinations thereof. For IgG2 such as chimeric, humanized or human IgG2, known mutations reducing FcγR binding include, but are not limited to: V234A, G237A, P238S, H268A, H268Q, A330S, P331S, P233S, V309L, and combinations thereof. For IgG3 such as chimeric, humanized or human IgG3, known mutations reducing FcγR binding include, but are not limited to: replacement of the CH2 domain of IgG3 with the CH2 domain of IgG2, removal of Fc glycosylation, mutations of L322, L276, N297, and combinations thereof. For IgG4 such as chimeric, humanized or human IgG4, known mutations reducing FcγR binding include, but are not limited to: V234A, L235E, LALA (Mutation of Leucine 234 to Alanine and Leucine 235 to Alanine), F234A, P329G, S228P, G237A, P238S, G236 deletion, and combinations thereof. The term “knob-into-hole” is well-known in the art. The knobs-into-hole is a well-established heterodimerization technology for the third constant domain of an antibody. The knob is typically formed by introducing a bulky amino acid (Tyr) at position 366 (EU numbering), while the hole is formed by replacing a bulky amino acid (Tyr) at position 407 with a smaller one (Thr). The knob fits into the hole of the oppositechain, resulting in a stable and specific heterodimeric Fc region. Similarly, FC3C1 / FCkC mutations are knownfrom Richter F, Seifert O, Herrmann A, Pfizenmaier K, Kontermann RE. Improved monovalent TNF receptor 1-selective inhibitor with novel heterodimerizing Fc. MAbs. 2019 May / Jun;11(4):653-665, which is incorporated herein by reference for all purposes. An “fusion protein construct” according to the invention may a fusion protein construct which is derivatized or linked to a different molecule. For example, molecules that may be linked to the fusion protein construct are a molecular label (e.g., a fluorescent, luminescent, colored, or radioactive molecule) and / or a pharmaceutical agent. The term “ligand of said receptor” as used herein is well-known in the art and will be understood by the skilled person as a molecule that binds to the indicated receptor. Ligands to the receptors referred to herein are known in the art and include, for instance, naturally occurring protein and peptide ligands and engineered amino acid sequence variants of naturally occurring protein and peptide ligands. In accordance with the present invention, the term "comprise" and variations of the term (e.g., “comprising”, “having”, “including”, “containing”), are not intended to exclude other technical features, additives, components, or steps. Furthermore, the word "comprise" encompasses the case of "consisting of". Each occurrence of the term “comprising” or variations of the term may optionally be substituted with the term “consisting of”. Methods and Techniques Generally, unless otherwise defined herein, the methods used in the present invention (e.g., cloning methods or methods relating to antibodies) are performed in accordance with procedures known in the art, e.g., the procedures described in Sambrook et al. (“Molecular Cloning: A Laboratory Manual.”, 2nd Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York 1989), Ausubel et al. (“Current Protocols in Molecular Biology.” Greene Publishing Associates and Wiley Interscience; New York 1992), and Harlow and Lane (“Antibodies: A Laboratory Manual” Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York 1988), all of which are incorporated herein by reference. Protein-protein binding, such as binding of antibodies to their respective target proteins or binding of the fusion protein constructs of the invention to their target proteins (e.g., the antigens referred to in connection with the domain iii) referred to herein or the receptors referred to in connection with the domain ii) referred to herein), can be assessed by methods known in the art. Protein-protein binding is preferably assessed by ELISA or surface plasmon resonance spectroscopy measurements or binding assays as with Gaussia princeps luciferase fusion proteins as described in Zaitseva et al (Zaitseva O, Anany M, Wajant H, Lang I. Basic characterization of antibodies targeting receptors of the tumor necrosis factor receptor superfamily. Front Immunol.2023 Mar 27;14:1115667; incorporated herein by reference for all purposes), for antibodies and VHH fusion proteins.As used herein, a domain (e.g., VHH or scFv) “competing” with another domain (e.g., VHH or scFv) for specificbinding to a target (e.g., an antigen referred to in connection with the domain iii) referred to herein or areceptor referred to in connection with the domain ii) referred to herein) means that said first-mentioned domainwhich is “competing” is capable to reduce the binding of a pre-bound 10 nM reference solution of the second-mentioned domain to the target by 50%. Generally, “competing” means that the concentration of the first-mentioned domain that is needed in order to reduce the binding of the pre-bound 10 nM reference solution of the second-mentioned domain to the target by 50% is less than 1000 nM, preferably less than 100 nM and more preferably less than 10 nM. The binding is preferably measured by Enzyme-linked Immunosorbent assay (ELISA) measurements. Sequence Alignments of sequences according to the invention are performed by using the BLAST algorithm(see Altschul et al. (1990) “Basic local alignment search tool.” Journal of Molecular Biology 215. p.403-410.;Altschul et al.: (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res.25:3389-3402.). Appropriate parameters for sequence alignments of short peptides by the BLAST algorithm, which are suitable for peptide antigens in accordance with the invention, are known in the art. Most software tools using the BLAST algorithm automatically adjust the parameters for sequence alignments for a short input sequence. In one embodiment, the following parameters are used: Max target sequences 10; Word size 3; BLOSUM 62 matrix; gap costs: existence 11, extension 1; conditional compositional score matrix adjustment. Thus, when used in connection with sequences, terms such as “identity” or “identical” preferably refer to the identity value obtained by using the BLAST algorithm. Preparation of pharmaceutical compositions of the Invention Pharmaceutical compositions of the present invention are prepared in accordance with known standards for the preparation of pharmaceutical compositions. For instance, the pharmaceutical compositions are prepared in a way that they can be stored and administered appropriately. The pharmaceutical compositions of the invention may therefore comprise pharmaceutically acceptable components such as carriers, excipients and / or stabilizers. Such pharmaceutically acceptable components are not toxic in the amounts used when administering the pharmaceutical composition to a human patient. The pharmaceutical acceptable components added to the pharmaceutical compositions may depend on the chemical nature of the active ingredients present in the composition, the particular intended use of the pharmaceutical compositions and the route of administration. In general, the pharmaceutically acceptable components used in connection with the present invention are used in accordance with knowledge available in the art, e.g., from Remington's Pharmaceutical Sciences, Ed.AR Gennaro, 20th edition, 2000, Williams & Wilkins, PA, USA. Sequences Preferred amino acid sequences referred to in the present application can be independently selected from the following sequences. The sequences are represented in an N-terminal to C-terminal order; and they are represented in the one-letter amino acid code. The following non-limiting exemplary amino acid sequences were used in the experimental examples of the present application and / or are disclosed herein as preferred amino acid sequences in accordance with the invention:(1) = Leader-R1-CL(2) = Leader-R1-CL-R3(3) = Leader-R2-(CH1-CH3) or Leader-R2-(CH1) (Fab) or Leader-R2-(CH1)-hinge (Fab2); whereby CH1-CH3 can be derived of any IgG or mutated IgG(4) = Leader-R2-(CH1-CH3)-R4 or Leader-R2-(CH1)-R4; whereby CH1-CH3 can be derived of any IgG ormutated IgG Note that “Leader” denotes a leader peptide which is used for expression but is typically removed / absent in the fusion protein constructs of the invention. Exemplary fusion protein constructs according to the invention can be formed by any combination of (1) or (2) with (3) or (4) whereby R1 = any X of table 1 or 2 below, R2 = any X of table1 or 2 below, R3 = any X of table1 or 2 below, R4 = any X of table 1 or 2 below, wherein at least one R (at least one of R1 to R4) is in accordance with domain ii) of claim 1 and is selected from Table 1 and at least one other R (at least one other of R1 to R4) is in accordance with domain iii) of claim 1 and is selected from Table 1 or 2. Table 1: exemplary amino acid sequences of the one or more binding domains according to claim 1 ii). XName Encoded AA sequence (SEQ ID NO)1 VHH:41BB QVQLVESGGGVVQPGRSLRLSCAASGSTFSIVAMGWYRQAPGKQRELVASIITGDGDTNYADSVKGRFTISRDNSKNTMYLQMNSL KPEDTAVYYCYARTGYGSSWLMGHEYDYWGQGTQVTVSSLG (SEQ ID NO:1)VHH:41BB(A-Ye-19) QVQLQESGGGLVQAGGSLRLSCAASGFSLGLYAIGWFRQAPGKEREWVSCIMSSDSSAYYADSVKGRFTVSRDNAKNTVYLQMN RLKPEDTAVYYCAAPQSDCFHYSENDYWGQGTQVTVSS (SEQ ID NO: 2)VHH:41BB(Yr13u14) QVQLQESGGGLVQAGDSLRLSCAASGSTFSIVAMGWYRQAPGKQRELVASIITGDGDTNYADSVKGRFTISRDNAKNTMYLQMNSL KPEDTAVYYCYARTGYGSSWLMGHEYDYWGQGTQVTVSS (SEQ ID NO: 3)VHH:CD40(V12t) QVQLQESGGGLVQAGGSLRLSCAASGLVFKRYSMNWYRQPPGQQRGLVASISDSGVSTNYADSVKGRFTISRDNAKNIGYLQMN SLKPEDTAVYYCNMHTFWGQGTQVTVSS (SEQ ID NO: 5)VHH:CD40(1B6) EVQLQESGGGLVQPGGSLRLSCVASGLHFDAAVMSWVRQAPGKGMEWVSSIYSYDRKTYYAASVRGRFTLSTNNAKNTMYLQM DNLKAEDTAIYYCAGDGAVAGSANRDDYQYWGQGTQVTVSS (SEQ ID NO: 6)VHH:CD40(1E10) EVQLVESGGGLVQPGGSLRLSCVASGSTLDYTAIGWFRQVPGKEREWVSCITASGGSTRSADSVKGRFTISRDNAKNTVYLQMNS LKPEDTAVYYCAKSRLLTRSCVSVDDYWGQGTQVTVSS (SEQ ID NO: 7)2xVHH:CD40(V12t) QVQLQESGGGLVQAGGSLRLSCAASGLVFKRYSMNWYRQPPGQQRGLVASISDSGVSTNYADSVKGRFTISRDNAKNIGYLQMN SLKPEDTAVYYCNMHTFWGQGTQVTVSSRSGGGGSGGGGSG GGGSGGGGSGGGGSQVQLQESGGGLVQAGGSLRLSCAASG LVFKRYSMNWYRQPPGQQRGLVASISDSGVSTNYADSVKGRF TISRDNAKNIGYLQMNSLKPEDTAVYYCNMHTFWGQGTQVTVS SGGGGSGGGGSGGGGSGGGGSGGGGS (SEQ ID NO: 8)VHH:GITR(C06) EVQLLESGGGEVQPGGSLRLSCAASGSVFSIDAMGWYRQAPGKGLELVSALSGISSATYAESVKGRFTISRDNAKNTLYLQMSSLR AEDTAVYYCYADVSTGWGRDAHGYWGQGTLVTV (SEQ ID NO: 9)VHH:OX40(V1) EVQLLESGGGEVQPGGSLRLSCAASGFTFSDAFMYWVRQAPGKGLEWVSSISNRGLKTAYAESVKGRFTISRDNAKNTLYLQMSSL RAEDTAVYYCSRDVDGDFRGQGTLVTVKP (SEQ ID NO: 10)scFv:41BB(HBBK4) QVQLQQSGAEVIKPGASVKLSCKASGYTFSSYWMHWVRQAPGQGLEWIGEINPGNGHTNYNEKFKSRATLTGDTSTSTVYMELS SLRSEDTAVYYCARSFTTARAFAYWGQGTLVTVSSRSSTKGPK LEEGEFSEAQLDIVMTQSPAFLSVTPGEKVTITCRASQTISDYLH WYQQKPDQAPKLLIKYASQSISGIPSRFSGSGSGTDFTFTISSLE AEDAATYYCQDGHSFPPTFGQGTKLEIK (SEQ ID NO: 21)scFv:CD30(cAC10) QIQLQQSGPEVVKPGASVKISCKASGYTFTDYYITWVKQKPGQGLEWIGWIYPGSGNTKYNEKFKGKATLTVDTSSSTAFMQLSSL TSEDTAVYFCANYGNYWFAYWGQGTQVTVSARSSTKGPKLEE GEFSEAQLDIVLTQSPASLAVSLGQRATISCKASQSVDFDGDSY MNWYQQKPGQPPKVLIYAASNLESGIPARFSGSGSGTDFTLNI HPVEEEDAATYYCQQSNEDPWTFGGGTKLEIK (SEQ ID NO: 23)scFv:CD40(G28.5) DIVMTQNPLSLPVSLGDEASISCRSSQSLENSNGNTFLNWFFQKPGQSPQLLIYRVSNRFSGVPDRFSGSGSGTDFTLKISRVEAE DLGVYFCLQVTHVPYTFGGGTTLEIKGGGGSGGGGSGGGGSD IQLQQSGPGLVKPSQSLSLTCSVTGYSITTNYNWNWIRQFPGN KLEWMGYIRYDGTSEYTPSLKNRVSITRDTSMNQFFLRLTSVTP EDTATYYCARLDYWGQGTLVTVSS (SEQ ID NO: 24)scFv:CD40(C) QVQLVQSGAEVKKPGASVKVSCTASGFNIKDYYVHWVKQAPGQGLEWMGRIDPEDGDSKYAPKFQGKATMTADTSTSTVYMELS SLRSEDTAVYYCTTSYYVGTYGYWGQGTLVTVSSRSSTKGPKL EEGEFSEAQLDIQMTQSPSSLSASVGDRVTITCSASSSVSYML WFQQKPGKAPKLLIYSTSNLASGVPSRFSGSGSGTDFTLTISSL QPEDFATYYCQQRTFYPYTFGGGTKVEIK (SEQ ID NO: 25)VHH:TNFR2(C188) DVQLVESGGGSVQTGGSLTLSCAISGSTSERYCLGWFRQAPGREREGVAATSLTGRGAQFYADSVKGRFTISLDDAKNTLYLQMD SLRPDDTAVYYCAEDVGFLCGYDSDNDPFYDWGQGTQVTVSS GASA (SEQ ID NO: 29)VHH: TNFR2(C238) QVQLVESGGGSVQPGGSLTLSCVDSGSAYLSYCMAWFRQAPGKEREGVAAIYYGGDSYYADSVKGRFTISQDHAKNTMYLQMN SLKPEDTAVYYCAADVGFICGYDSDNDPPNDWGQGTQVTVSS GASA (SEQ ID NO: 30)VHH:CD30(1G5-48-86) EVQLVESGGGLVQAGGSLRLSCADSGSTFSMNVMGWYRQAPGKQQRELVAAIGSGVGTTVYGDSVKGRFTISRDNTKNTMYLQM NSLKAEDTAVYYCNAARRFEELGYNYQGYWGQGTQVTVSSEP KTPKPQT (SEQ ID NO: 31)scFv:TNFR2(C4) QVQLLQSGPELVKPGASVKLSCKASGYSFTSYDINWVKQRPGQGLEWVGWIYPRDGDTKYNEKFKGKAILTVDTSSNTAYMNLHS LTSEDSAVYFCARLTGPYWYFDVWGTGTTVTVSSRSSTKGPKL EEGEFSEAQLDIVMTQSHKFMSTSVGDRVSITCKASQDVDTAV AWYQQKPGQSPKLLIYWASTRHTGVPDRFTGSGSGTDYTLTIS SVQAEDLARYYCQQYYSVPPTFGGGTKLEIK (SEQ ID NO: 38)2xVHH:TNFR2(C188) DVQLVESGGGSVQTGGSLTLSCAISGSTSERYCLGWFRQAPGREREGVAATSLTGRGAQFYADSVKGRFTISLDDAKNTLYLQMD SLRPDDTAVYYCAEDVGFLCGYDSDNDPFYDWGQGTQVTVSS RSGGGGSGGGGSGGGGSGGGGSGGGGSDVQLVESGGGSV QTGGSLTLSCAISGSTSERYCLGWFRQAPGREREGVAATSLTG RGAQFYADSVKGRFTISLDDAKNTLYLQMDSLRPDDTAVYYCA EDVGFLCGYDSDNDPFYDWGQGTQVTVSS (SEQ ID NO: 40) 40 3xVHH:TNFR2(C188) DVQLVESGGGSVQTGGSLTLSCAISGSTSERYCLGWFRQAPGREREGVAATSLTGRGAQFYADSVKGRFTISLDDAKNTLYLQMD SLRPDDTAVYYCAEDVGFLCGYDSDNDPFYDWGQGTQVTVSS RSGGGGSGGGGSGGGGSGGGGSGGGGSDVQLVESGGGSV QTGGSLTLSCAISGSTSERYCLGWFRQAPGREREGVAATSLTG RGAQFYADSVKGRFTISLDDAKNTLYLQMDSLRPDDTAVYYCA EDVGFLCGYDSDNDPFYDWGQGTQVTVSSGGGGSGGGGSG GGGSGGGGSGGGGSQLDVQLVESGGGSVQTGGSLTLSCAIS GSTSERYCLGWFRQAPGREREGVAATSLTGRGAQFYADSVK GRFTISLDDAKNTLYLQMDSLRPDDTAVYYCAEDVGFLCGYDS DNDPFYDWGQGTQVTVSSGASA (SEQ ID NO: 41) 41 VHH:CD40mu(JPP-G1) QVQLVESGGGLVQPGGSLRLSCVASGFTFNGDTMIWYRQTPGKTREWVAGIAPIGDIANYANSVKGRFTISRDNAKNTVYLQMNSL RPEDTAVYYCNTVTWGQSNSYWGQGTQVTVSSEPKTPKPQ (SEQ ID NO: 42) Table 2: exemplary amino acid sequences of the one or more binding domains according to claim 1 iii). XName Encoded AA sequence (SEQ ID NO)4 VHH:BCMA(269…) AVQLVESGGGLVQAGDSLRLTCTASGRAFSTYFMAWFRQAPGKEREFVAGIAWSGGSTAYADSVKGRFTISRDNAKNTVYLQMNS LKSEDTAVYYCASRGIEVEEFGAWGQGTQVTVSS (SEQ ID NO: 4) 11 VHH:B7-H3(B12) QVQLVESGGGSVQVGGSLRLSCAASGFTYNSYSVGWFRQAPGKEREGVAAINSGGSSTYYAASVKGRFTISRDNAKNTVYLQMN SLKPEDTAMYYCAARSPSPLTFQTRTLREDSYNYWGQGTQVT VSS (SEQ ID NO: 11) 12 VHH:B7-H3(G8) DVQLVESGGGLVQPGGSLRLSCAASGFTFSRYWMGWFRQAPGKGVEWVSTINSGGGSTYYADSVKGRFTISRDNAKNTLYLQLN NLKTEDTAMYYCAKEQWRTGSRGQGTQVTVSS (SEQ ID NO: 12) 13 VHH:CTLA4(Seq120) QVQLVESGGGLVQPGGSLRLSCAASGYIYSAYCMGWFRQAPGKGLVGVAAISIGGGSTYYADSVKGRFTISRDNSKNTLYLQMNSL RAEDTAVYYCAADVIPTETCLGGSWSGPFGYWGQGTLVTVSS (SEQ ID NO: 13)VHH:EGFR(7D12) QVKLEESGGGSVQTGGSLRLTCAASGRTSRSYGMGWFRQAPGKEREFVSGISWRGDSTGYADSVKGRFTISRDNAKNTVDLQM NSLKPEDTAIYYCAAAAGSAWYGTLYEYDYWGQGTQVTVSS (SEQ ID NO: 14)VHH:FAP(4G3) QVQFVESGGGLVQPGGSLRLSCAASGSIVSVGFMGWYRQAPGKKRELVAGISTYSDDINVVDSVKGRFTISRDNAKNTVFLQMSS LKPEDTAVYYCSEVPPRIGQNWGQGTQVTVSS (SEQ ID NO: 15)VHH:FAP(3C4) QVQFVESGGGLVQPGGSLRLSCAASGNIVNSYTMGWYRQALGKQREYVAFITTDGMTNYASSVKGRFTISRDNAKNTVDLHMNSL KPEDTAVYYCNRSPPGVSNYWGQGTQVTVSS (SEQ ID NO: 16)VHH:CXCR4(238D4) EVQLMESGGGLVQAGGSLRLSCAASGRTFNNYAMGWFRRAPGKEREFVAAITRSGVRSGVSAIYGDSVKDRFTISRDNAKNTLYL QMNSLKPEDTAVYTCAASAIGSGALRRFEYDYSGQGTQVTVSS (SEQ ID NO: 17)VHH:PDL1 EVQLQESGGGLVQPGGSLRLSCAASGFTFSSYWMYWLRQAPGKGLEWVSSINSDSSSTYYRDSVKGRFTISRDNAKNTLYLQMN SLKSEDTAVYYCAKDPGGYAKGQGTQVTVSSD (SEQ ID NO: 18)VHH:PD1(102C3) EVQLVESGGGLVQAGKSLRLSCAASGSIFSIHAMGWFRQAPGKEREFVAAITWSGGITYYEDSVKGRFTISRDNAKNTVYLQMNSLK PEDTAIYYCAADRAESSWYDYWGQGTQVTVSS (SEQ ID NO: 19)VHH:PSMA(JVZ-007) EVQLVESGGGLVQPGGSLTLSCAASRFMISEYSMHWVRQAPGKGLEWVSTINPAGTTDYAESVKGRFTISRDNAKNTLYLQMNSLK PEDTAVYYCDGYGYRGQGTQVTVSS (SEQ ID NO: 20)scFv:BCMA(C11D53) DIVLTQSPASLAMSLGKRATISCRASESVSVIGAHLIHWYQQKPGQPPKLLIYLASNLETGVPARFSGSGSGTDFTLTIDPVEEDDVAI YSCLQSRIFPRTFGGGTKLEIKGSTSGSGKPGSGEGSTKGQIQL VQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKW MGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDT ATYFCALDYSYAMDYWGQGTSVTVSS (SEQ ID NO: 22)scFv:CD70(9G2) QVQLVESGGGLMQPGGSLRLSCAASGFTFSSSAMSWVRQAPGKGLEWVSSIYSDSSYTYYADSVKSRFTISTDNAKNTLYLQMNS LKPDDTAVYYCAGSSDYEGSFASWGQGTQVTVSSRSSTKGPK LEEGEFSEAQLQSVVTQPPSLSASPGSSVRLTCTLSSGNSVGN YDISWYQQKAGSPPRYLLYYYSDSVKHQGSGVPSRFSGSSDA SANAGLLLISGLQPEDEADYYCSAYKSGSHVFGGGTKLTVLG (SEQ ID NO: 26)scFv:CD70(2H5) QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYIMHWVRQAPGKGLEWVAVISYDGRNKYYADSVKGRFTISRDNSKNTLYLQMNS LRAEDTAVYYCARDTDGYDFDYWGQGTLVTVSSGGGGSGGG GSGGGGSEIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWY QQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEP EDFAVYYCQQRTNWPLTFGGGTKVEIKASTKG (SEQ ID NO: 27)scBAFF GPEETVTQDCLQLIADSETPTIQKGSYTFVPWLLSFKRGSALEEKENKILVKETGYFFIYGQVLYTDKTYAMGHLIQRKKVHVFGDEL SLVTLFRCIQNMPETLPNNSCYSAGIAKLEEGDELQLAIPRENA QISLDGDVTFFGALKLLGGGGSGGGGSGPEETVTQDCLQLIAD SETPTIQKGSYTFVPWLLSFKRGSALEEKENKILVKETGYFFIYG QVLYTDKTYAMGHLIQRKKVHVFGDELSLVTLFRCIQNMPETLP NNSCYSAGIAKLEEGDELQLAIPRENAQISLDGDVTFFGALKLLG GGGSGGGGSQFAAGPEETVTQDCLQLIADSETPTIQKGSYTFV PWLLSFKRGSALEEKENKILVKETGYFFIYGQVLYTDKTYAMGH LIQRKKVHVFGDELSLVTLFRCIQNMPETLPNNSCYSAGIAKLEE GDELQLAIPRENAQISLDGDVTFFGALKLL (SEQ ID NO: 28)scTNF80(mu) EFTRDKPVAHVVANHQVEEQLEWLSQRANALLANGMDLKDNQLVVPADGLYLVYSQVLFKGQGCPDYVLLTHTVSRFAISYQEKVN LLSAVKSPCPKDTPEGAELKPWYEPIYLGGVFQLEKGDQLSAE VNLPKYLNFRESGQVYFGVIALGGGSGGGSGGGSGGGSDKPV AHVVANHQVEEQLEWLSQRANALLANGMDLKDNQLVVPADGL YLVYSQVLFKGQGCPDYVLLTHTVSRFAISYQEKVNLLSAVKSP CPKDTPEGAELKPWYEPIYLGGVFQLEKGDQLSAEVNLPKYLN FRESGQVYFGVIALGGGSGGGSGGGSGGGSDKPVAHVVANH QVEEQLEWLSQRANALLANGMDLKDNQLVVPADGLYLVYSQV LFKGQGCPDYVLLTHTVSRFAISYQEKVNLLSAVKSPCPKDTPE GAELKPWYEPIYLGGVFQLEKGDQLSAEVNLPKYLNFRESGQV YFGVIAL (SEQ ID NO: 37)VHH:CD38(JK36) QVQLQESGGGLVQPGGSLRLSCAASGIILRIYDMGWYRQAPGKQRELVAAITSRGSTNYADSVKGRFTISRDNAENTVSLQMNSLKP GDTAVYYCNADHTFAGVYWGQGTQVTVSS (SEQ ID NO: 43)VHH:CD38(MU1067) DVQLQESGGGLVQAGDSLRLSCVGSGRRFDNYAMAWFRQAPGKERTFVAAISWSSGTTRYLDTVKGRFTISRDNAKSTVYLQMN SLKPEDTAVYYCAARYQPRYYDSGDMDGYEYEFWGQGTQVT VSS (SEQ ID NO: 44)VHH:CD25(A02)(block) QVQLVESGGGLVQPGGSLRLSCATSGFTFRNNFMSWVRQAPGKGLEWVSTISYGGESTTYAESVKGRFTISRDNAKNTLYLQMN NLKPEDTAVYYCAKATSYDSIRSGSRGQGTQVTVSS (SEQ ID NO: 45) 45 VHH:CD25(G01)(nonblock) EVQLVESGGGLVQAGGSLRLSCAASGGSIYTYNMGWFRQAPG KEREFVAGTLWSGGDSVYADFAKGRFTLSRENAKNTLYLQMN SLKPEDTATYYCAIDPLSLTSDWRVDELSSWGKGTLVTVSS (SEQ ID NO: 46) 46 IL2(ed) APTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEELKPLEEVLNLAQSKNFHLRPRDLISNIN VIVLELKGSETTFMCEYADETATIVEFLNRWITFCQSIISTLT (SEQ ID NO: 47) 47 VHH:CD30(1G5-48-86) EVQLVESGGGLVQAGGSLRLSCADSGSTFSMNVMGWYRQAPGKQQRELVAAIGSGVGTTVYGDSVKGRFTISRDNTKNTMYLQM NSLKAEDTAVYYCNAARRFEELGYNYQGYWGQGTQVTVSSEP KTPKPQT (SEQ ID NO: 48)Table 3: exemplary amino acid sequences of the constant domains of the fusion protein constructs accordingto the invention, which form part of the scaffold domain according to i) of claim 1. Name Encoded AA sequence (SEQ ID NO)32 CL (Constant light chain) EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKV YACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 32) 33 CH1-CH3(wt) SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK TKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 33) 34 CH1-CH3(N297A) SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK TKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 34) 35 CH1-FAB1 SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHT (SEQ ID NO: 35)36 CH1-FAB2 SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPA (SEQ ID NO: 36) Any amino acid sequences of the constant domains of the fusion protein constructs according to the invention may optionally contain an additional amino acid tag suitable for purification such as a Flag tag (DYKDDDDK; SEQ ID NO: 39) The inventors have found that advantageously, If one of the Rs of any combination of (1) or (2) with (3) or (4) is a VHH specific for a receptor as defined in domain ii) referred to herein (i.e., TNFR2, CD40, 41BB, CD27, OX40, GITR, Fn14, CD30, BCMA or RANK), the resulting fusion protein construct is regularly highly produced, non-aggregated and typically act as a conditional TNFR agonist with activity dependent on binding to the cell surface or extracellular matrix antigen(s) recognized by the remaining “R(s)”. If two of the Rs of any combination of (1) or (2) with (3) or (4) are VHHs specific for a receptor as defined in domain ii) referred to herein, the resulting fusion protein construct is regularly highly produced, non- aggregated and typically acts as a conditional TNFR agonist with weak intrinsic agonism and strong additional activity dependent on binding to the cell surface or extracellular matrix antigen(s) recognized by the remaining “R(s)” (the one or more domains according to iii) referred to herein). If two of the Rs of any combination of (1) or (2) with (3) or (4) are VHHs specific for two different receptors as defined in domain ii) referred to herein, the resulting construct is regularly highly produced, non- aggregated and typically acts as a conditional TNFR agonist with dual TNFR agonistic activity dependent on co-binding of both TNFR types or dependent on binding to the cell surface or extracellular matrix antigen(s) recognized by the remaining “R(s)” (the one or more domains according to iii) referred to herein). If three or all four of the Rs of any combination of (1) or (2) with (3) or (4) are VHHs specific for different receptors as defined in domain ii) referred to herein, the resulting construct is regularly highly produced, non- aggregated and typically act as a conditional TNFR agonist with TNFR agonistic activity dependent on co- binding of at least two TNFR types or dependent on binding to the cell surface or extracellular matrix antigen recognized by the remaining “R” (the domain according to iii) referred to herein). If one of the Rs is a scFv or an autonomous non-antibody peptide domain instead of a VHH, the resulting constructs have similar functional properties but the expression level of the constructs become more variable (scFv variants typically still excellent, autonomous non-antibody peptide very variable). If two of the Rs are scFv or an autonomous non-antibody peptide domain instead of a VHH, the resulting constructs can have similar functional properties but the expression level of the constructs is often lower and especially with scFv domains there is incidence of aggregation. Valency and number of specificities can be increased when one or more of the “Rs” are VHH-VHH or VHH- VHH-VHH cassettes of any combination of X instead of VHH only domains. Thus, in one embodiment, the fusion protein construct does not comprise any scFv fragment. Such a fusion protein construct is highly expressed and does not aggregate. In one embodiment, the fusion protein construct does not comprise more than one scFv fragment. Such a fusion protein construct has similar functional properties compared to other fusion protein constructs according to the invention comprising no scFv fragment, but such a fusion protein construct may have a more variable expression level. In one embodiment, the fusion protein construct does not comprise more than two scFv fragments. Such a fusion protein construct has similar functional properties compared to other fusion protein constructs according to the invention comprising less scFv fragments, but such fusion protein constructs have frequently a lower expression level and some aggregation. In one embodiment, the fusion protein construct comprises two binding domains according to ii), binding to two different receptors selected from the group consisting of TNFR2, CD40, 41BB, CD27, OX40, GITR, Fn14, CD30, BCMA and RANK, and each of the two binding domains are one VHH domain. In one embodiment, the fusion protein construct comprises three or four binding domains according to ii), binding to three or four different receptors selected from the group consisting of TNFR2, CD40, 41BB, CD27, OX40, GITR, Fn14, CD30, BCMA and RANK, and each of the three or four binding domains are one VHH domain. EXAMPLES The present invention is further illustrated by the following non-limiting examples. Material and Methods Production and purification of fusion proteins Fusion proteins were produced by transient transfection of HEK293 cells by the PEI method (PEI, polyethylenimine; Polyscience Inc., Warrington, USA) using 1:1 mixtures of the expression plasmids encoding the antibody heavy and light chain variants of interest (for details see Kums et al., 2017 (29)). To control size and chain balance and to estimate the concentration of the various TNFR1-targeting antibody fusion proteins, 10 µl of the supernatant of the cells producing the construct of interest were analysed by anti-Flag western blotting with the Flag tag-specific antibody M2 (Sigma-Aldrich, Saint Louis, USA) exploiting the fact that all antibody chain variants used were cloned with an N-terminal Flag tag. The concentrations of the fusion proteins were estimated by comparison with an in parallel processed in house produced Flag- tagged control antibody of known concentration. For purification by affinity chromatography on anti-Flag M2 agarose (Sigma-Aldrich, Steinheim, Germany), the supernatants containing the Flag-tagged fusion proteins and the anti-Flag agarose column(s) were prepared as described by the supplier and described in Fick et al., 2012 (30). After binding of the Flag-tagged constructs the anti-Flag M2 agarose gel, the columns were washed with TBS and the remaining proteins bound were eluted using a buffer with an excess of Flag® peptide (100 µg / ml). The eluted fusion proteins were dialyzed against PBS to reduce the Flag® peptide content. Coculture assays to determine TNFR activation by analysing TNFR target gene production To quantify TNFR activation by the various TNFR-targeting antibody fusion proteins, their ability to stimulate the production of cytokines known to be strongly induced by TNFR via the classical NFκB signaling pathway in certain cell lines (“responder cells”), was determined. For this purpose, variants of the human cell HT1080 stably transfected with expression plasmids encoding CD40, TNFR2, GITR, 41BB, BCMA or OX40 and HT1080 cells expressing endogenously Fn14 were used which produce in response to TNFR stimulation high levels of IL8. The responder cells were cultivated overnight in 96-well plates (2 X 104cells / well) and the next day medium was replaced with fresh medium supplemented with HEK293 cells (2 X 104cells / well) transfected with empty vector or expression vectors encoding human proteins serving as anchoring targets for the binding domains according to iii) of claim 1 along with the TNFR-targeting antibody fusion proteins of interest according to ii) of claim 1. In some experiments human cell lines with endogenous expression of the anchoring target (AT) (Jurkat – endogenous CXCR4, LnCAP –endogenous PSMA, BJAB – endogenous CD70, A431 – endogenous EGFR) or stable AT-transfectants (Jurkat-PD1, B16-FAP) of interest along with AT-negative cell lines or control transfectants (Jurkat, B16) were used instead of HE293 transfectants. After an additional overnight cultivation, the amount of IL8 in the supernatant, as an indicator of TNFR activity was determined using commercially available ELISA kits for IL8 (BD Biosciences, San Diego, USA). OD values were measured with a PHOmo photometer (46nthos Mikrosysteme GmbH, Friesoythe, Germany) and normalized by help of cytokines of known concentrations processed ion parallel. Results Conditional anchoring target (AT)-restricted TNFR activation by the various TNFR-targeting antibody fusion proteins was quantified by measuring their ability to stimulate the production of the cytokine IL8 known to be strongly induced by TNFRs via the classical NFκB signaling pathway in certain cell lines (“TNFR responder cells”). To this end, HEK293 cells which were either transfected with empty vector (EV) or an expression plasmid encoding the protein serving as anchoring target (AT) for a fusion protein construct according to the invention were added to human HT1080 cell variants expressing the TNFR of interest and which produce high amounts of IL8 in response to activation of this receptor as TNFR responder cell lines. Alternatively, cell lines with endogenous expression of the anchoring target (AT) (Jurkat – endogenous CXCR4, LnCAP –endogenous PSMA, BJAB – endogenous CD70, A431 – endogenous EGFR) or stable AT- transfectants (Jurkat-PD1, B16-FAP) of interest along with AT-negative cell lines or control transfectants (Jurkat, B16) were added to the HT1080 responder cell variant. The examples of the TNFR-targeting antibody fusion proteins shown, all induced strong IL8 production in the co-cultures of the corresponding appropriate HT1080 variant and AT-expressing cells while there was no or only very moderate IL8 induction in co-cultures of the corresponding appropriate HT1080 variant and AT-negative cells. The conditional PDL1-restricted CD40 agonists shown in figure 3 were obtained either by coexpression of an amino acid chain comprising a VHH of irrelevant specificity, the CL (table 3, sequence 32) as part of the CAD and one copy of sequence 18 of table 2 along with an amino acid chain comprising the CD40-specific VHH of table 1 (sequence 5) and the CH1 (table 3, sequence 35) as part of the CAD (left panel) or by coexpression of an amino acid chain comprising the CD40-specific VHH of sequence 5 from table 1, the CL (table 3, sequence 32) as part of the CAD and one copy of sequence 18 of table 2 along with the already mentioned amino acid chain comprising the CD40-specific VHH of table 1 (sequence 5) and the CH1 (table 3, sequence 35) as part of the CAD (right panel). In each case VHH domains were connected with the CAD domains by a GGGGS linker . The conditional FAP-restricted CD40 agonist shown in figure 4 was obtained by coexpression of an amino acid chain comprising the CD40-specific VHH of sequence 5 from table 1, the CL (table 3, sequence 32) as part of the CAD and the FAP-specific VHH of table 2, sequence 16 along with an amino acid chain comprising again the CD40-specific VHH of table 1, sequence 5 and the CH1 (table 3, sequence 35) as part of the CAD. The VHH domains were connected with the CAD domains by a GGGGS linker. The conditional TNFR2-binding dependent CD40 agonists shown in figure 5 were obtained by coexpression of an amino acid chain comprising sequence 41 of table 1 (VHH specific for murine CD40), the CL (table3, sequence 32) as part of the CAD and the TNFR2-specific VHH of sequence 29 of table 1 and amino acid chains comprising the 2xVHH and 3xVHH sequences 40 and 41 of table 1 followed in both cases by the CH1 (table 3, sequence 35) as part of the CAD. The VHH domains were connected with the CAD domains by a GGGGS linker. The conditional GITR-, BCMA-, PDL1-, 41BB- and PD1-restricted CD40 agonists shown in figure 10 were obtained by coexpression of an amino acid chain comprising sequence 5 of table 1 followed by sequence 32 of table 3 and amino acid chains comprising sequence 9 (table 2), sequence 4 (table 2), sequence 18 (table 2), sequence 1 (table 1) or sequence 19 (table 2) followed in each case by sequence 34 of table 3. The conditional FAP-, PSMA-, CXCR4- and EGFR-restricted CD40 agonists shown in figure 11 were obtained by coexpression of an amino acid chain comprising sequence 5 of table 1 followed by sequence 32 of table 3 and amino acid chains comprising sequence 15 (table 2), sequence 20 (table 2), sequence 17 (table 2), or sequence 14 (table 2) followed in each case by sequence 34 of table 3. The conditional CD30-restricted CD40 agonist shown in figure 12 was obtained by coexpression of an amino acid chain comprising sequence 23 of table 1 followed by sequence 32 of table 3 and an amino acid chain comprising sequence 5 of table 1 followed by sequence 34 of table 3. The conditional BCMA-restricted CD40 agonist shown in figure 12 was obtained by coexpression of an amino acid chain comprising sequence 5 of table 1 followed by sequence 32 of table 3 and an amino acid chain comprising sequence 22 of table 2 followed by sequence 34 of table 3. The conditional PDL1-restricted CD40 agonist shown in figure 13 were obtained by coexpression of amino acid chains comprising sequence 6 of table 1 or sequence 7 of table 1 followed in both cases by sequence 32 of table 3 and an amino acid chain comprising sequence 18 of table 2 followed by sequence 34 of table 3. The conditional BCMA- and PSMA-restricted CD40 agonists shown in figure 14 were obtained by coexpression of an amino acid chain comprising sequence 24 of table 1 followed by sequence 32 of table 3 and amino acid chains comprising sequence 4 of table 2 or sequence 20 of table 2 followed in both cases by sequence 34 of table 3. The conditional PDL1-restricted CD40 agonists shown in figure 14 were obtained by coexpression of an amino acid chain comprising sequence 18 of table 2 followed by sequence 32 of table 3 and an amino acid chain comprising sequence 25 of table 1 followed by sequence 34 of table 3. The conditional PDL1-, BCMA- and PD1-restricted CD40 agonists shown in figure 15 were obtained by coexpression of an amino acid chain comprising sequence 5 of table 1 followed by sequence 32 of table 3 and amino acid chains comprising sequence 5 of table 1 followed by sequence 34 of table 3 and sequence 18 (table 2) or sequence 4 (table 2) or sequence 19 (table 2). The conditional CD70- and Baff receptors (BaffR)-restricted CD40 agonists shown in figure 16 were obtained by coexpression of an amino acid chain comprising sequence 5 of table 1 followed by sequence 32 of table 3 and amino acid chains comprising sequence 5 of table 1 followed by sequence 34 of table 3 and sequence 27 (table 2) or sequence 28 (table 2). The conditional PSMA-, CXCR4-, PDL1- and PD1-restricted CD40 agonists shown in figure 17 were obtained by coexpression of an amino acid chain comprising two copies of sequence 5 of table 1 connected by a GGGGS linker followed by sequence 32 of table 3 and amino acid chains comprising sequence 20 of table 2 or sequence 17 of table 2 or sequence 18 of table 2 or sequence 19 of table 2 followed by sequence 34 of table 3 in each case. The conditional PDL1-restricted 41BB agonists shown in figure 18 were obtained by coexpression of an amino acid chain comprising sequence 18 of table 2 followed by sequence 32 of table 3 and amino acid chains comprising sequence 2 of table 1 or sequence 3 of table 1 followed in both cases by sequence 34 of table 3. The conditional BCMA-restricted 41BB agonists shown in figure 18 were obtained by coexpression of an amino acid chain comprising sequence 4 of table 2 followed by sequence 32 of table 3 and amino acid chains comprising sequence 2 of table 1 or sequence 3 of table 1 followed in both cases by sequence 34 of table 3. The conditional PDL1- and / or CTLA4-binding dependent OX40 agonist shown in figure 19 were obtained by coexpression of an amino acid chain comprising sequence 13 of table 2 followed by sequence 32 of table 3 and sequence 10 of table 1 and an amino acid chain comprising sequence 18 of table 2 followed by sequence 34 of table 3. The conditional PDL1- and / or BCMA-binding dependent 41BB agonist shown in figure 20 was obtained by coexpression of an amino acid chain comprising sequence 18 of table 2 followed by sequence 32 of table 3 and sequence 1 of table 1 and an amino acid chain comprising sequence 4 of table 2 followed by sequence 34 of table 3. The conditional PDL1- and / or BCMA-binding dependent OX40 agonist shown in figure 20 was obtained by coexpression of an amino acid chain comprising sequence 18 of table 2 followed by sequence 32 of table 3 and sequence 10 of table 1 and an amino acid chain comprising sequence 4 of table 2 followed by sequence 34 of table 3. The conditional CXCR4-binding dependent GITR agonist shown in figure 21 were obtained by coexpression of an amino acid chain comprising sequence 9 of table 1 followed by sequence 32 of table 3 and an amino acid chain comprising sequence 17 of table 2 followed by sequence 34 of table 3. The conditional CD40-, PDL1- and BCMA-restricted 41BB agonist shown in figure 22 were obtained by coexpression of an amino acid chain comprising sequence 21 of table 1 followed by sequence 32 of table 3 and an amino acid chain comprising sequence 5 of table 1 or sequence 18 of table 2 or sequence 4 of table 2 followed in all three cases by sequence 34 of table 3. The conditional OX40- and / or BCMA-binding dependent, OX40- and / or CXCR4-binding dependent, OX40- and / or FAP-binding dependent, OX40- and / or PSMA-binding dependent and OX40- and / or PD1-binding dependent CD40 agonists shown in figure 23 were obtained by coexpression of an amino acid chain comprising sequence 5 of table 1 followed by sequence 32 of table 3 and sequence 10 of table 1 and amino acid chains comprising sequence 4 of table 2 or sequence 17 of table 2 or sequence 16 of table 2 or sequence 20 of table 2 or sequence 19 of table 2 followed in all five cases by sequence 34 of table 3. The conditional OX40- and / or BCMA-binding dependent, OX40- and / or CXCR4-binding dependent, OX40- and / or FAP-binding dependent, OX40- and / or PSMA-binding dependent and OX40- and / or PD1-binding dependent CD40 agonists shown in figure 24 were obtained by coexpression of an amino acid chain comprising sequence 10 of table 1 followed by sequence 32 of table 3 and sequence 5 of table 1 and amino acid chains comprising sequence 4 of table 2 or sequence 17 of table 2 or sequence 16 of table 2 or sequence 20 of table 2 or sequence 19 of table 2 followed in all five cases by sequence 34 of table 3. The conditional 41BB- and / or BCMA-binding dependent and 41BB- and / or PDL1-binding dependent CD40 agonists shown in figure 25 were obtained by coexpression of amino acid chains comprising sequence 5 of table 1 followed by sequence 32 of table 3 and either sequence 1 of table 1 or sequence of 18 of table 2 and an amino acid chain comprising sequence 5 of table 1 followed by sequence 34 of table 3 and sequence 4 of table 2. The conditional PDL1- and / or PD1-binding dependent CD40 agonists shown in figure 25 was obtained by coexpression of an amino acid chain comprising sequence 5 of table 1 followed by sequence 32 of table 3 and sequence 18 of table 2 and an amino acid chain comprising sequence 5 of table 1 followed by sequence 34 of table 3 and sequence 19 of table 2. The conditional BCMA- or PDL1-restricted dual CD40 and OX40 agonist shown in figure 26 were obtained by coexpression of amino acid chains comprising sequence 5 of table 1 followed by sequence 32 of table 3 and sequence 10 of table 1 and amino acid chains comprising sequence 5 of table 1 followed by sequence 34 of table 3 and either sequence 4 of table 2 or sequence 18 of table 2. The conditional PDL1-restricted dual CD40 and 41BB agonist shown in figure 27 was obtained by coexpression of an amino acid chain comprising sequence 5 of table 1 followed by sequence 32 of table 3 and sequence 1 of table 1 and an amino acid chain comprising sequence 5 of table 1 followed by sequence 34 of table 3 and sequence 18 of table 2. The conditional 41BB and / or Baff receptors (BaffR)-binding dependent, OX40 and / or Baff receptors (BaffR)- binding dependent and PDL1 and / or Baff receptors (BaffR)-binding dependent CD40 agonists shown in figure 28 were obtained by coexpression of amino acid chains comprising sequence 5 of table 1 followed by sequence 32 of table 3 and sequence 1 of table 1 or sequence 10 of table 1 or sequence 18 of table 2 and an amino acid chain comprising sequence 5 of table 1 followed by sequence 34 of table 3 and sequence 28 of table 2. The conditional PSMA- and / or CD70-binding dependent, CXCR4- and / or CD70-dependent and BCMA- and / or CD70-binding dependent CD40 agonists shown in figure 29 were obtained by coexpression of an amino acid chain comprising sequence 5 of table 1 followed by sequence 32 of table 3 and amino acid chains comprising sequence 20 of table 2 or sequence 17 of table 2 or sequence 4 of table 2 followed by sequence 34 of table 3 and sequence 26 of table 2. The conditional CXCR4- and / or CD70-binding dependent, PD1- and / or CD70-dependent and PSMA- and / or CD70-binding dependent CD40 agonists shown in figure 30 were obtained by coexpression of an amino acid chain comprising sequence 17 of table 2 or sequence 19 of table 2 or sequence 20 of table 2 followed in all three cases by sequence 32 of table 3 and sequence 26 of table 2 along with an amino acid chain comprising sequence 5 of table 1 followed by sequence 34 of table 3. The conditional PD1-binding dependent TNFR2 agonist shown in figure 32 were obtained by coexpression of an amino acid chain comprising sequence 29 of table 1 followed by sequence 32 of table 3 and an amino acid chain comprising sequence 19 of table 2 followed by sequence 34 of table 3. The conditional TNFR2- and / or 41BB-binding dependent CD40 agonist shown in figure 33 was obtained by coexpression of an amino acid chain comprising sequence 5 of table 1 followed by sequence 32 of table 3 and sequence 1 of table 1 and an amino acid chain comprising sequence 5 of table 1 followed by sequence 34 of table 3 and sequence 29 of table 1. The reciprocally conditional CD40 and 41BB, CD40 and GITR, and CD40 and TNFR2 agonists shown in figure 34 were obtained by coexpression of an amino acid chain comprising sequence 5 of table 1 followed by sequence 32 of table 3 and amino acid chains comprising sequence 1 of table 1 or sequence 9 of table 1 or sequence 29 of table 1 followed by sequence 34 of table 3. The reciprocally conditional GITR and TNFR2 agonist shown in figure 34 was obtained by coexpression of an amino acid chain comprising sequence 9 of table 1 followed by sequence 32 of table 3 and an amino acid chain comprising sequence 29 of table 1 followed by sequence 34 of table 3. The reciprocally conditional 41BB and TNFR2, and CD40 and TNFR2 agonists shown in figure 35 were obtained by coexpression of an amino acid chain comprising sequence 1 of table 1 or sequence 5 of table 1 both followed by sequence 32 of table 3 and an amino acid chain comprising sequence 38 of table 1 followed by sequence 34 of table 3. The reciprocally conditional TNFR2 and CD40 agonist shown in figure 35 was obtained by coexpression of an amino acid chain comprising sequence 38 of table 1 followed by sequence 32 of table 3 and an amino acid chain comprising sequence 5 of table 1 followed by sequence 34 of table 3. The mutually reciprocally conditional CD40-, 41BB- and TNFR2 agonist shown in figure 36 was obtained by coexpression of an amino acid chain comprising sequence 1 of table 1 followed by sequence 32 of table 3 and an amino acid chain comprising sequence 5 of table 1 followed by sequence 34 of table 3 and sequence 29 of table 1. The mutually reciprocally conditional TNFR2-, CD40- and GITR agonist shown in figure 36 was obtained by coexpression of an amino acid chain comprising sequence 9 of table 1 followed by sequence 32 of table 3 and an amino acid chain comprising sequence 29 of table 1 followed by sequence 34 of table 3 and sequence 5 of table 1. The conditional CD40 agonists shown in figure 37 were obtained by coexpression of an amino acid chain comprising sequence 11, 42, 43, 44, 45, or 47 of table 2 followed by sequence 32 of table 3 and an amino acid chain comprising sequence 5 or 6 of table 1 followed by sequence 34 of table 3. With exception of VHH:TNFR2(C188)-VHH:CXCR4(238D4)-IgG1(N297A), the conditional TNFR2 agonists shown in figure 38 were obtained by coexpression of an amino acid chain comprising sequence 16, 44 or 45 of table 2 followed by sequence 32 of table 3 and the amino acid chain comprising sequence 29 of table 1 followed by sequence 34 of table 3. Furthermore, VHH:TNFR2(C188)-VHH:CXCR4(238D4)-IgG1(N297A) was obtained by coexpression of an amino acid chain comprising sequence 29 of table 1 followed by sequence 32 of table 3 and the amino acid chain comprising sequence 17 of table 2 followed by sequence 34 of table 3. The dual reciprocal conditional TNFR2 / CD40 agonists shown in figure 39 were obtained either by coexpression of the amino acid chain comprising sequence 29 of table 1 followed by sequence 32 of table 3 and the amino acid chain comprising sequence 5 of table 1 followed by sequence 34 of table 3 (left panel) or by coexpression of the amino acid chain comprising sequence 5 of table 1 followed by sequence 32 of table 3 and the amino acid chain comprising sequence 29 of table 1 followed by sequence 34 of table 3 (right panel). The trispecific conditional CD40 agonists shown in figure 40 were obtained by coexpression of the amino acid chain comprising sequence 5 of table 1 followed by sequence 32 of table 3 and an amino acid chain comprising sequence 44 or 45 of table 2 followed by sequence 34 of table 3 and sequence 19 again from table 2. The dual reciprocal conditional TNFR2 / CD40 agonists with additional CD25-restricted TNFR2- and CD40 agonism shown in figure 41 were obtained either by coexpression of the amino acid chain comprising sequence 46 of table 1 followed by sequence 32 of table 3 and the amino acid chain comprising sequence 5 of table 1 followed by sequence 34 of table 3 and sequence 29 again of table 1 or by coexpression of the amino acid chain comprising sequence 46 of table 1 followed by sequence 32 of table 3 and the amino acid chain comprising sequence 29 of table 1 followed by sequence 34 of table 3 and sequence 5 again of table 1. The dual reciprocal conditional TNFR2 / CD40 agonists with additional PDL1-restricted TNFR2- and CD40 agonism shown in figure 42 were obtained either by coexpression of the amino acid chain comprising sequence 29 of table 1 followed by sequence 32 of table 3 and the amino acid chain comprising sequence 5 of table 1 followed by sequence 34 of table 3 and sequence 18 of table 2 or by coexpression of the amino acid chain comprising sequence 29 of table 1 followed by sequence 32 of table 3 and sequence 18 of table 2 and the amino acid chain comprising sequence 5 of table 1 followed by sequence 34 of table 3 or by coexpression of the amino acid chain comprising sequence 29 of table 1 followed by sequence 32 of table 3 and sequence 18 of table 2 and the amino acid chain comprising sequence 5 of table 1 followed by sequence 34 and sequence 18 of table 2. The trispecific conditional CD40 agonist shown in figure 43 was obtained by coexpression of the amino acid chain comprising sequence 46 of table 2 followed by sequence 32 of table 3 and an amino acid chain comprising sequence 16 of table 2 followed by sequence 34 of table 3 and sequence 5 from table 1. The trispecific conditional CD40 agonists shown in figure 44 were obtained by coexpression of the amino acid chains comprising sequence 17 or 20 of table 2 followed by sequence 32 of table 3 and amino acid chains comprising sequence 5 of table 1 followed by sequence 34 of table 3 and sequences 19 or 22 from table 2. The tetraspecific conditional CD40 agonists shown in figure 45 were obtained by coexpression of the amino acid chain comprising sequence 5 of table 1 followed by sequence 32 of table 3 and sequence 17 of table 2 along with the amino acid chains comprising sequence 5 of table 1 followed by sequence 34 of table 3 and sequences 19 or 22 from table 2. The conditional CD40 agonists shown in figure 46 were obtained either by coexpression of the amino acid chain comprising sequence 5 of table 1 followed by sequence 32 of table 3 and the amino acid chains comprising sequence 5 of table 1 followed by sequence 34 of table 3 and sequences 16, 17, 20 or 22 from table 2 or by coexpression of the amino acid chain comprising sequence 5 of table 1 followed by sequence 32 of table 3 and the sequence 16, 17, 20 or 22 from table 2 along with the amino acid chain comprising sequence 5 of table 1 followed by sequence 34 of table 3 or by coexpression of the amino acid chain comprising sequence 5 of table 1 followed by sequence 32 of table 3 and the sequence 16, 17, 20 or 22 from table 2 along with the amino acid chains comprising sequence 5 of table 1 followed by sequence 34 of table 3 and sequences 16, 17, 20 or 22 from table 2 whereby amino chains were chosen pairwise with either sequence 16, 17, 20 or 22 domains. INDUSTRIAL APPLICABILITY The pharmaceutical compositions, polypeptides, nucleic acids, cells, and products for use in the invention are industrially applicable. For example, they can be used in the manufacture of, or as, pharmaceutical products. REFERENCESRef. 1: Periodic-Table-of-Antibodies (retrieved from https: / / absoluteantibody.com / periodic-table-of-antibodies-download / on the 19.01.2024) Ref. 2: Labrijn, A. F., Janmaat, M. L., Reichert, J. M., & Parren, P. W. (2019). Bispecific antibodies: a mechanistic review of the pipeline. Nature reviews Drug discovery, 18(8), 585-608. Ref.3: Nie, S., Wang, Z., Moscoso-Castro, M., D'Souza, P., Lei, C., Xu, J., & Gu, J. (2020). Biology drives the discovery of bispecific antibodies as innovative therapeutics. Antibody therapeutics, 3(1), 18-62. Ref.4: Brinkmann, U., & Kontermann, R. E. (2017, February). The making of bispecific antibodies. In MAbs (Vol.9, No.2, pp.182-212). Taylor & Francis. Ref.5: Chanier, T., & Chames, P. (2019). Nanobody engineering: toward next generation immunotherapies and immunoimaging of cancer. Antibodies, 8(1), 13.

Claims

1. CLAIMS1. An at least bispecific fusion protein construct comprising:i) a scaffold domain comprising the constant portion of an Fab fragment comprising (1) a CH1domain and (2) a CLdomain, ii) one or more binding domains binding to a receptor selected from the group consisting ofTNFR2, CD40, 41BB, CD27, OX40, GITR, Fn14, CD30, BCMA and RANK, or a combination thereof, wherein the one or more binding domains are selected from the group consisting of a VHH, an scFv fragment, a ligand of said receptor, and a combination of two or more of a VHH, an scFv fragment, and a ligand of said receptor, and iii) one or more binding domains binding to a cell surface antigen or an extracellular matrixantigen which is different from the receptor bound by the one or more binding domains according to ii), wherein the binding domains according to ii) and iii) are covalently linked to at least one N- terminus and / or to at least one C-terminus of the scaffold domain according to i), and each binding domain according to ii) is covalently linked to a different N- or C-terminus of the scaffold domain according to i) than the one or more binding domains according to iii).

2. The fusion protein construct according to claim 1, wherein the scaffold domain consists of theconstant portion of the Fab fragment consisting of (1) the CH1 domain, wherein the CH1 domain has preferably the amino acid sequence of SEQ ID NO: 35, and (2) the CLdomain, wherein the CLdomain has preferably the amino acid sequence of SEQ ID NO: 32.

3. The fusion protein construct according to claim 1, wherein the scaffold domain comprises theconstant portion of an F(ab’)2fragment comprising two constant portions of Fab’ fragments, each of these portions comprising: (1) a CH1 domain followed by a hinge region and (2) a CLdomain.

4. The fusion protein construct according to claim 3, wherein the scaffold domain consists of theconstant portion of the F(ab’)2fragment consisting of the two constant portions of Fab’ fragments, each of these portions consisting of: (1) the CH1 domain followed by the hinge region, wherein the CH1 domain followed by the hinge region has preferably the amino acid sequence of SEQ ID NO: 36, and (2) the CLdomain, wherein the CLdomain has preferably the amino acid sequence of SEQ ID NO: 32.

5. The fusion protein construct according to claim 1 or 3, wherein the scaffold domain comprisesan immunoglobulin lacking the VHand VLregions.

6. The fusion protein construct according to claim 5, wherein the scaffold domain consists of animmunoglobulin lacking the VHand VLregions, and wherein the immunoglobulin lacking the VHand VLregions preferably consists of: a) an immunoglobulin heavy chain lacking the VHregion, wherein the immunoglobulin heavy chain lacking the VHregion preferably has the amino acid sequence of SEQ ID NO: 33 or 34, and b) a CLdomain, wherein the CLdomain preferably has the amino acid sequence of SEQ ID NO: 32.

7. The fusion protein construct according to claim 1, 3 or 5, wherein the scaffold domain comprisesa full-length immunoglobulin.

8. The fusion protein construct according to claim 7, wherein the scaffold domain consists of a full-length immunoglobulin.

9. The fusion protein construct according to any one of the preceding claims, comprising a seriesof 2 or 3 binding domains according to ii) in a linear polypeptide chain, wherein the series is preferably a series of binding domains, preferably VHH domains, binding to the same receptor.

10. The fusion protein construct according to any one of the preceding claims, comprising a seriesof 2 or 3 binding domains according to iii) in a linear polypeptide chain, wherein the series is preferably a series of binding domains, preferably VHH domains, binding to the same cell surface antigen or extracellular matrix antigen.

11. The fusion protein construct according to any one of the preceding claims, wherein said cellsurface antigen or extracellular matrix antigen is a cell surface antigen.

12. The fusion protein construct according to any one of the preceding claims, wherein said cellsurface antigen or extracellular matrix antigen is a protein.

13. The fusion protein construct according to any one of the preceding claims, wherein said cellsurface antigen or extracellular matrix antigen is a tumor antigen.

14. The fusion protein construct according to any one of the preceding claims, wherein said cellsurface antigen or extracellular matrix antigen is a human antigen.

15. The fusion protein construct according to any one of the preceding claims, wherein said cellsurface antigen is an antigen of an immune cell, optionally wherein the immune cell is a human immune cell, further optionally wherein the human immune cell is a human T lymphocyte.

16. The fusion protein construct according to any one of the preceding claims, wherein said cellsurface antigen or extracellular matrix antigen is selected from the group consisting of CD40, CD30, BCMA, B7-H3, CTLA4, EGFR, FAP, CXCR4, PDL1, PD1, PSMA, CD70, CD25, the high affinity and low affinity IL-2 receptor complex, CD38 and BAFF.

17. The fusion protein construct according to any one of the preceding claims, wherein said cellsurface antigen or extracellular matrix antigen is CD40 and the one or more binding domains according to ii) are selected from the group consisting of a binding domain binding to a receptor selected from TNFR2, 41BB, CD27, OX40, GITR, Fn14, CD30, BCMA and RANK, or a combination thereof.

18. The fusion protein construct according to any one of the preceding claims, wherein said cellsurface antigen or extracellular matrix antigen is CD30 and the one or more binding domains according to ii) are selected from the group consisting of a binding domain binding to a receptor selected from TNFR2, CD40, 41BB, CD27, OX40, GITR, Fn14, BCMA and RANK, or a combination thereof.

19. The fusion protein construct according to any one of the preceding claims, comprising onebinding domain according to ii), wherein the binding domain according to ii) is a VHH.

20. The fusion protein construct according to any one of claims 1 to 18, comprising two bindingdomains according to ii) binding to the same receptor, wherein each of the two binding domainsaccording to ii) are a VHH domain, or the two binding domains according to ii) are a series of 2 VHH domains in a linear polypeptide chain.

21. The fusion protein construct according to any one of claims 1 to 18, comprising two bindingdomains according to ii) binding to two different receptors selected from the group consisting of TNFR2, CD40, 41BB, CD27, OX40, GITR, Fn14, CD30, BCMA and RANK, and wherein each of the two binding domains are one VHH domain.

22. The fusion protein construct according to any one of claims 1 to 18, comprising three or fourbinding domains according to item 1 ii) binding to three or four different receptors selected from the group consisting of TNFR2, CD40, 41BB, CD27, OX40, GITR, Fn14, CD30, BCMA and RANK, and wherein each of the three or four binding domains are one VHH domain.

23. The fusion protein construct according to any one of claims 1 to 18, comprising three bindingdomains according to ii) binding to the same receptor, wherein each of the three binding domains according to ii) are a VHH domain, or the three binding domains according to ii) are a series of 3 VHH domains in a linear polypeptide chain.

24. The fusion protein construct according to any one of claims 1 to 18, comprising four bindingdomains according to ii) binding to the same receptor, and wherein each of the four binding domains according to ii) are a VHH domain, or the four binding domains according to ii) are a VHH domain and a series of 3 VHH domains in a linear polypeptide chain.

25. The fusion protein construct according to any of the preceding claims, wherein the scaffolddomain is from an IgG molecule, preferably from a human IgG1, IgG2, IgG3 or IgG4 molecule.

26. The fusion protein construct of any one of claims 5 to 25, wherein the full-length immunoglobulinof the scaffold domain or the immunoglobulin of the scaffold domain lacking the VHand VLregions contains a mutation modifying FcγR binding, preferably a mutation reducing FcγR binding.

27. The fusion protein construct of any one of claims 5 to 26, wherein the mutation is an N297Amutation.

28. The fusion protein construct of any one of claims 5 to 27, wherein the full-length immunoglobulinof the scaffold domain or the immunoglobulin lacking the VHand VLregions of the scaffold domain is a knob-into-hole immunoglobulin or contains a FC3C1 / FCkC mutation.

29. The fusion protein construct according to any one of the preceding claims, wherein the one ormore binding domains according to ii) are selected from one or more of the following: a0) an anti-41BB VHH; a1) an anti-41BB VHH having the amino acid sequence of SEQ ID NO: 1; a2) an anti-41BB VHH competing with the anti-41BB VHH of a1) for specific binding to 41BB; a3) an anti-41BB VHH having the same CDRs as the anti-41BB VHH of a1); anda4) an anti-41BB VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 1, at least 90% identical to the amino acid sequence of SEQ ID NO: 1, at least 95% identical to the amino acid sequence of SEQ ID NO: 1, at least 98% identical tothe amino acid sequence of SEQ ID NO: 1, or at least 99% identical to the amino acid sequence of SEQ ID NO: 1 and preferably having the same CDRs as the anti-41BB VHH of a1); b1) an anti-41BB VHH having the amino acid sequence of SEQ ID NO: 2; b2) an anti-41BB VHH competing with the anti-41BB VHH of b1) for specific binding to 41BB;b3) an anti-41BB VHH having the same CDRs as the anti-41BB VHH of b1); andb4) an anti-41BB VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 2, at least 90% identical to the amino acid sequence of SEQ ID NO: 2, at least 95% identical to the amino acid sequence of SEQ ID NO: 2, at least 98% identical to the amino acid sequence of SEQ ID NO: 2, or at least 99% identical to the amino acid sequence of SEQ ID NO: 2 and preferably having the same CDRs as the anti-41BB VHH of b1); c1) an anti-41BB VHH having the amino acid sequence of SEQ ID NO: 3; c2) an anti-41BB VHH competing with the anti-41BB VHH of c1) for specific binding to 41BB;c3) an anti-41BB VHH having the same CDRs as the anti-41BB VHH of c1); andc4) an anti-41BB VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 3, at least 90% identical to the amino acid sequence of SEQ ID NO: 3, at least 95% identical to the amino acid sequence of SEQ ID NO: 3, at least 98% identical to the amino acid sequence of SEQ ID NO: 3, or at least 99% identical to the amino acid sequence of SEQ ID NO: 3 and preferably having the same CDRs as the anti-41BB VHH of c1); d0) an anti-CD40 VHH; d1) an anti-CD40 VHH having the amino acid sequence of SEQ ID NO: 5; d2) an anti-CD40 VHH competing with the anti-CD40 VHH of d1) for specific binding to CD40;d3) an anti-CD40 VHH having the same CDRs as the anti-CD40 VHH of d1); andd4) an anti-CD40 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 5, at least 90% identical to the amino acid sequence of SEQ ID NO: 5, at least 95% identical to the amino acid sequence of SEQ ID NO: 5, at least 98% identical to the amino acid sequence of SEQ ID NO: 5, or at least 99% identical to the amino acid sequence of SEQ ID NO: 5 and preferably having the same CDRs as the anti-CD40 VHH of d1); e1) an anti-CD40 VHH having the amino acid sequence of SEQ ID NO: 6; e2) an anti-CD40 VHH competing with the anti-CD40 VHH of e1) for specific binding to CD40;e3) an anti-CD40 VHH having the same CDRs as the anti-CD40 VHH of e1); ande4) an anti-CD40 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 6, at least 90% identical to the amino acid sequence of SEQ ID NO: 6, at least 95% identical to the amino acid sequence of SEQ ID NO: 6, at least 98% identical to the amino acid sequence of SEQ ID NO: 6, or at least 99% identical to the amino acid sequence of SEQ ID NO: 6 and preferably having the same CDRs as the anti-CD40 VHH of e1);f1) an anti-CD40 VHH having the amino acid sequence of SEQ ID NO: 7; f2) an anti-CD40 VHH competing with the anti-CD40 VHH of f1) for specific binding to CD40;f3) an anti-CD40 VHH having the same CDRs as the anti-CD40 VHH of f1); andf4) an anti-CD40 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 7, at least 90% identical to the amino acid sequence of SEQ ID NO: 7, at least 95% identical to the amino acid sequence of SEQ ID NO: 7, at least 98% identical to the amino acid sequence of SEQ ID NO: 7, or at least 99% identical to the amino acid sequence of SEQ ID NO: 7 and preferably having the same CDRs as the anti-CD40 VHH of f1); g0) a series of 2 anti-CD40 VHH domains in a linear polypeptide chain; g1) a series of 2 anti-CD40 VHH domains in a linear polypeptide chain, the linear polypeptide chain having the amino acid sequence of SEQ ID NO: 8; g2) an anti-CD40 VHH competing with the anti-CD40 VHH of g1) for specific binding to CD40;g3) an anti-CD40 VHH having the same CDRs as the anti-CD40 VHH of g1); andg4) an anti-CD40 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 8, at least 90% identical to the amino acid sequence of SEQ ID NO: 8, at least 95% identical to the amino acid sequence of SEQ ID NO: 8, at least 98% identical to the amino acid sequence of SEQ ID NO: 8, or at least 99% identical to the amino acid sequence of SEQ ID NO: 8 and preferably having the same CDRs as the anti-CD40 VHH of g1); h0) an anti-GITR VHH; h1) an anti-GITR VHH having the amino acid sequence of SEQ ID NO: 9; h2) an anti-GITR VHH competing with the anti-GITR VHH of h1) for specific binding to GITR;h3) an anti-GITR VHH having the same CDRs as the anti-GITR VHH of h1); andh4) an anti-GITR VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 9, at least 90% identical to the amino acid sequence of SEQ ID NO: 9, at least 95% identical to the amino acid sequence of SEQ ID NO: 9, at least 98% identical to the amino acid sequence of SEQ ID NO: 9, or at least 99% identical to the amino acid sequence of SEQ ID NO: 9 and preferably having the same CDRs as the anti-GITR VHH of h1); i0) an anti-OX40 VHH; i1) an anti-OX40 VHH having the amino acid sequence of SEQ ID NO: 10; i2) an anti-OX40 VHH competing with the anti-OX40 VHH of i1) for specific binding to OX40;i3) an anti-OX40 VHH having the same CDRs as the anti-OX40 VHH of i1); andi4) an anti-OX40 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 10, at least 90% identical to the amino acid sequence of SEQ ID NO: 10, at least 95% identical to the amino acid sequence of SEQ ID NO: 10, at least 98% identical to the amino acid sequence of SEQ ID NO: 10, or at least 99% identical to the amino acid sequence of SEQ ID NO: 10 and preferably having the same CDRs as the anti-OX40 VHH of i1);j0) an anti-41BB scFv; j1) an anti-41BB scFv having the amino acid sequence of SEQ ID NO: 21; j2) an anti-41BB scFv competing with the anti-41BB scFv of j1) for specific binding to 41BB;j3) an anti-41BB scFv having the same CDRs as the anti-41BB scFv of j1); andj4) an anti-41BB scFv having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 21, at least 90% identical to the amino acid sequence of SEQ ID NO: 21, at least 95% identical to the amino acid sequence of SEQ ID NO: 21, at least 98% identical to the amino acid sequence of SEQ ID NO: 21, or at least 99% identical to the amino acid sequence of SEQ ID NO: 21 and preferably having the same CDRs as the anti-41BB scFv of j1); k0) an anti-CD30 scFv; k1) an anti-CD30 scFv having the amino acid sequence of SEQ ID NO: 23; k2) an anti-CD30 scFv competing with the anti-CD30 scFv of k1) for specific binding to CD30;k3) an anti-CD30 scFv having the same CDRs as the anti-CD30 scFv of k1); andk4) an anti-CD30 scFv having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 23, at least 90% identical to the amino acid sequence of SEQ ID NO: 23, at least 95% identical to the amino acid sequence of SEQ ID NO: 23, at least 98% identical to the amino acid sequence of SEQ ID NO: 23, or at least 99% identical to the amino acid sequence of SEQ ID NO: 23 and preferably having the same CDRs as the anti-CD30 scFv of k1); l0) an anti-CD40 scFv; l1) an anti-CD40 scFv having the amino acid sequence of SEQ ID NO: 24; l2) an anti-CD40 scFv competing with the anti-CD40 scFv of l1) for specific binding to CD40;l3) an anti-CD40 scFv having the same CDRs as the anti-CD40 scFv of l1); andl4) an anti-CD40 scFv having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 24, at least 90% identical to the amino acid sequence of SEQ ID NO: 24, at least 95% identical to the amino acid sequence of SEQ ID NO: 24, at least 98% identical to the amino acid sequence of SEQ ID NO: 24, or at least 99% identical to the amino acid sequence of SEQ ID NO: 24 and preferably having the same CDRs as the anti-CD40 scFv of l1); m1) an anti-CD40 scFv having the amino acid sequence of SEQ ID NO: 25; m2) an anti-CD40 scFv competing with the anti-CD40 scFv of m1) for specific binding to CD40;m3) an anti-CD40 scFv having the same CDRs as the anti-CD40 scFv of m1); andm4) an anti-CD40 scFv having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 25, at least 90% identical to the amino acid sequence of SEQ ID NO: 25, at least 95% identical to the amino acid sequence of SEQ ID NO: 25, at least 98% identicalto the amino acid sequence of SEQ ID NO: 25, or at least 99% identical to the amino acid sequence of SEQ ID NO: 25 and preferably having the same CDRs as the anti-CD40 scFv of m1); n0) an anti-TNFR2 VHH; n1) an anti-TNFR2 VHH having the amino acid sequence of SEQ ID NO: 29; n2) an anti-TNFR2 VHH competing with the anti-TNFR2 VHH of n1) for specific binding to TNFR2;n3) an anti-TNFR2 VHH having the same CDRs as the anti-TNFR2 VHH of n1); andn4) an anti-TNFR2 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 29, at least 90% identical to the amino acid sequence of SEQ ID NO: 29, at least 95% identical to the amino acid sequence of SEQ ID NO: 29, at least 98% identical to the amino acid sequence of SEQ ID NO: 29, or at least 99% identical to the amino acid sequence of SEQ ID NO: 29 and preferably having the same CDRs as the anti-TNFR2 VHH of n1); o1) an anti-TNFR2 VHH having the amino acid sequence of SEQ ID NO: 30; o2) an anti-TNFR2 VHH competing with the anti-TNFR2 VHH of o1) for specific binding to TNFR2;o3) an anti-TNFR2 VHH having the same CDRs as the anti-TNFR2 VHH of o1); ando4) an anti-TNFR2 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 30, at least 90% identical to the amino acid sequence of SEQ ID NO: 30, at least 95% identical to the amino acid sequence of SEQ ID NO: 30, at least 98% identical to the amino acid sequence of SEQ ID NO: 30, or at least 99% identical to the amino acid sequence of SEQ ID NO: 30 and preferably having the same CDRs as the anti-TNFR2 VHH of o1);p0) an anti-TNFR2 scFv;p1) an anti-TNFR2 scFv having the amino acid sequence of SEQ ID NO: 38; p2) an anti-TNFR2 scFv competing with the anti-TNFR2 scFv of p1) for specific binding to TNFR2;p3) an anti-TNFR2 scFv having the same CDRs as the anti-TNFR2 scFv of p1); andp4) an anti-TNFR2 scFv having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 38, at least 90% identical to the amino acid sequence of SEQ ID NO: 38, at least 95% identical to the amino acid sequence of SEQ ID NO: 38, at least 98% identical to the amino acid sequence of SEQ ID NO: 38, or at least 99% identical to the amino acid sequence of SEQ ID NO: 38 and preferably having the same CDRs as the anti-TNFR2 scFv of p1);q0) a series of 2 anti-TNFR2 VHH domains in a linear polypeptide chain;q1) a series of 2 anti-TNFR2 VHH domains in a linear polypeptide chain, the linear polypeptide chain having the amino acid sequence of SEQ ID NO: 40; q2) an anti-TNFR2 VHH competing with the anti-TNFR2 VHH of q1) for specific binding to TNFR2; q3) an anti-TNFR2 VHH having the same CDRs as the anti-TNFR2 VHH of q1); and q4) an anti-TNFR2 VHH having an amino acid sequence at least 85% identical to the amino acid sequence of SEQ ID NO: 40, at least 90% identical to the amino acid sequence of SEQ ID NO: 40, at least 95% identical to the amino acid sequence of SEQ ID NO: 40, at least 98% identical to the amino acid sequence of SEQ ID NO: 40, or at least 99% identical to the amino acid sequence of SEQ ID NO: 40 and preferably having the same CDRs as the anti-TNFR2 VHH of q1); r0) a series of 3 anti-TNFR2 VHH domains in a linear polypeptide chain;r1) a series of 3 anti-TNFR2 VHH domains in a linear polypeptide chain, the linear polypeptide chain having the amino acid sequence of SEQ ID NO: 41; r2) an anti-TNFR2 VHH competing with the anti-TNFR2 VHH of r1) for specific binding to TNFR2; r3) an anti-TNFR2 VHH having the same CDRs as the anti-TNFR2 VHH of r1); andr4) an anti-TNFR2 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 41, at least 90% identical to the amino acid sequence of SEQ ID NO: 41, at least 95% identical to the amino acid sequence of SEQ ID NO: 41, at least 98% identical to the amino acid sequence of SEQ ID NO: 41, or at least 99% identical to the amino acid sequence of SEQ ID NO: 41 and preferably having the same CDRs as the anti-TNFR2 VHH of r1); and s1) an anti-CD40 VHH having the amino acid sequence of SEQ ID NO: 42; s2) an anti-CD40 VHH competing with the anti-CD40 VHH of s1) for specific binding to CD40; s3) an anti-CD40 VHH having the same CDRs as the anti-CD40 VHH of s1); ands4) an anti-CD40 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 42, at least 90% identical to the amino acid sequence of SEQ ID NO: 42, at least 95% identical to the amino acid sequence of SEQ ID NO: 42, at least 98% identical to the amino acid sequence of SEQ ID NO: 42, or at least 99% identical to the amino acid sequence of SEQ ID NO: 42 and preferably having the same CDRs as the anti-CD40 VHH of s1).

30. The fusion protein construct according to any one of the preceding claims, wherein the one ormore binding domains according to iii) are selected from one or more of the following:aa0) an anti-BCMA VHH; aa1) an anti-BCMA VHH having the amino acid sequence of SEQ ID NO: 4; aa2) an anti-BCMA VHH competing with the anti-BCMA VHH of aa1) for specific binding to BCMA;aa3) an anti-BCMA VHH having the same CDRs as the anti-BCMA VHH of aa1); andaa4) an anti-BCMA VHH having an amino acid sequence at least 85% identical to the aminoacid sequence of SEQ ID NO: 4, at least 90% identical to the amino acid sequence of SEQ ID NO: 4, at least 95% identical to the amino acid sequence of SEQ ID NO: 4, at least 98% identical to the amino acid sequence of SEQ ID NO: 4, or at least 99% identical to the amino acid sequence of SEQ ID NO: 4 and preferably having the same CDRs as the anti-BCMA VHH of aa1); bb0) an anti-B7-H3 VHH; bb1) an anti-B7-H3 VHH having the amino acid sequence of SEQ ID NO: 11; bb2) an anti-B7-H3 VHH competing with the anti-B7-H3 VHH of bb1) for specific binding to B7- H3;bb3) an anti-B7-H3 VHH having the same CDRs as the anti-B7-H3 VHH of bb1); andbb4) an anti-B7-H3 VHH having an amino acid sequence at least 85% identical to the aminoacid sequence of SEQ ID NO: 11, at least 90% identical to the amino acid sequence of SEQ ID NO: 11, at least 95% identical to the amino acid sequence of SEQ ID NO: 11, at least 98% identical to the amino acid sequence of SEQ ID NO: 11, or at least 99% identical to the amino acid sequence of SEQ ID NO: 11 and preferably having the same CDRs as the anti-B7-H3 VHH of bb1); cc1) an anti-B7-H3 VHH having the amino acid sequence of SEQ ID NO: 12; cc2) an anti-B7-H3 VHH competing with the anti-B7-H3 VHH of cc1) for specific binding to B7- H3;cc3) an anti-B7-H3 VHH having the same CDRs as the anti-B7-H3 VHH of cc1); andcc4) an anti-B7-H3 VHH having an amino acid sequence at least 85% identical to the aminoacid sequence of SEQ ID NO: 12, at least 90% identical to the amino acid sequence of SEQ ID NO: 12, at least 95% identical to the amino acid sequence of SEQ ID NO: 12, at least 98% identical to the amino acid sequence of SEQ ID NO: 12, or at least 99% identical to the amino acid sequence of SEQ ID NO: 12 and preferably having the same CDRs as the anti-B7-H3 VHH of cc1); dd0) an anti-CTLA4 VHH; dd1) an anti-CTLA4 VHH having the amino acid sequence of SEQ ID NO: 13; dd2) an anti-CTLA4 VHH competing with the anti-CTLA4 VHH of dd1) for specific binding to CTLA4;dd3) an anti-CTLA4 VHH having the same CDRs as the anti-CTLA4 VHH of dd1); anddd4) an anti-CTLA4 VHH having an amino acid sequence at least 85% identical to the aminoacid sequence of SEQ ID NO: 13, at least 90% identical to the amino acid sequence of SEQ ID NO: 13, at least 95% identical to the amino acid sequence of SEQ ID NO: 13, at least 98% identical to the amino acid sequence of SEQ ID NO: 13, or at least 99% identical to the amino acid sequence of SEQ ID NO: 13 and preferably having the same CDRs as the anti-CTLA4 VHH of dd1); ee0) an anti-EGFR VHH; ee1) an anti-EGFR VHH having the amino acid sequence of SEQ ID NO: 14; ee2) an anti-EGFR VHH competing with the anti-EGFR VHH of ee1) for specific binding to EGFR;ee3) an anti-EGFR VHH having the same CDRs as the anti-EGFR VHH of ee1); andee4) an anti-EGFR VHH having an amino acid sequence at least 85% identical to the aminoacid sequence of SEQ ID NO: 14, at least 90% identical to the amino acid sequence of SEQ ID NO: 14, at least 95% identical to the amino acid sequence of SEQ ID NO: 14, at least 98% identical to the amino acid sequence of SEQ ID NO: 14, or at least 99% identical to the amino acid sequence of SEQ ID NO: 14 and preferably having the same CDRs as the anti-EGFR VHH of ee1); ff0) an anti-FAP VHH; ff1) an anti-FAP VHH having the amino acid sequence of SEQ ID NO: 15; ff2) an anti-FAP VHH competing with the anti-FAP VHH of ff1) for specific binding to FAP;ff3) an anti-FAP VHH having the same CDRs as the anti-FAP VHH of ff1); andff4) an anti-FAP VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 15, at least 90% identical to the amino acid sequence of SEQ ID NO: 15, at least 95% identical to the amino acid sequence of SEQ ID NO: 15, at least 98% identical to the amino acid sequence of SEQ ID NO: 15, or at least 99% identical to the amino acid sequence of SEQ ID NO: 15 and preferably having the same CDRs as the anti-FAP VHH of ff1); gg1) an anti-FAP VHH having the amino acid sequence of SEQ ID NO: 16; gg2) an anti-FAP VHH competing with the anti-FAP VHH of gg1) for specific binding to FAP;gg3) an anti-FAP VHH having the same CDRs as the anti-FAP VHH of gg1); andgg4) an anti-FAP VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 16, at least 90% identical to the amino acid sequence of SEQ ID NO: 16, at least 95% identical to the amino acid sequence of SEQ ID NO: 16, at least 98% identical to the amino acid sequence of SEQ ID NO: 16, or at least 99% identical to the amino acid sequence of SEQ ID NO: 16 and preferably having the same CDRs as the anti-FAP VHH of gg1); hh0) an anti-CXCR4 VHH;hh1) an anti-CXCR4 VHH having the amino acid sequence of SEQ ID NO: 17; hh2) an anti-CXCR4 VHH competing with the anti-CXCR4 VHH of hh1) for specific binding to CXCR4;hh3) an anti-CXCR4 VHH having the same CDRs as the anti-CXCR4 VHH of hh1); andhh4) an anti-CXCR4 VHH having an amino acid sequence at least 85% identical to the aminoacid sequence of SEQ ID NO: 17, at least 90% identical to the amino acid sequence of SEQ ID NO: 17, at least 95% identical to the amino acid sequence of SEQ ID NO: 17, at least 98% identical to the amino acid sequence of SEQ ID NO: 17, or at least 99% identical to the amino acid sequence of SEQ ID NO: 17 and preferably having the same CDRs as the anti-CXCR4 VHH of hh1); ii0) an anti-PDL1 VHH; ii1) an anti-PDL1 VHH having the amino acid sequence of SEQ ID NO: 18; ii2) an anti-PDL1 VHH competing with the anti-PDL1 VHH of ii1) for specific binding to PDL1;ii3) an anti-PDL1 VHH having the same CDRs as the anti-PDL1 VHH of ii1); andii4) an anti-PDL1 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 18, at least 90% identical to the amino acid sequence of SEQ ID NO: 18, at least 95% identical to the amino acid sequence of SEQ ID NO: 18, at least 98% identical to the amino acid sequence of SEQ ID NO: 18, or at least 99% identical to the amino acid sequence of SEQ ID NO: 18 and preferably having the same CDRs as the anti-PDL1 VHH of ii1); jj1) an anti-PD1 VHH having the amino acid sequence of SEQ ID NO: 19; jj2) an anti-PD1 VHH competing with the anti-PD1 VHH of jj1) for specific binding to PD1;jj3) an anti-PD1 VHH having the same CDRs as the anti-PD1 VHH of jj1); andjj4) an anti-PD1 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 19, at least 90% identical to the amino acid sequence of SEQ ID NO: 19, at least 95% identical to the amino acid sequence of SEQ ID NO: 19, at least 98% identical to the amino acid sequence of SEQ ID NO: 19, or at least 99% identical to the amino acid sequence of SEQ ID NO: 19 and preferably having the same CDRs as the anti-PD1 VHH of jj1); kk0) an anti-PSMA VHH; kk1) an anti-PSMA VHH having the amino acid sequence of SEQ ID NO: 20; kk2) an anti-PSMA VHH competing with the anti-PSMA VHH of kk1) for specific binding to PSMA;kk3) an anti-PSMA VHH having the same CDRs as the anti-PSMA VHH of kk1); andkk4) an anti-PSMA VHH having an amino acid sequence at least 85% identical to the aminoacid sequence of SEQ ID NO: 20, at least 90% identical to the amino acid sequence of SEQ ID NO: 20, at least 95% identical to the amino acid sequence of SEQ ID NO: 20, at least 98% identical to the amino acid sequence of SEQ ID NO: 20, or at least 99% identical to the aminoacid sequence of SEQ ID NO: 20 and preferably having the same CDRs as the anti-PSMA VHH of kk1); ii0) an anti-BCMA scFv; ll1) an anti-BCMA scFv having the amino acid sequence of SEQ ID NO: 22; ll2) an anti-BCMA scFv competing with the anti-BCMA scFv of ll1) for specific binding to BCMA;ll3) an anti-BCMA scFv having the same CDRs as the anti-BCMA scFv of ll1); andll4) an anti-BCMA scFv having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 22, at least 90% identical to the amino acid sequence of SEQ ID NO: 22, at least 95% identical to the amino acid sequence of SEQ ID NO: 22, at least 98% identical to the amino acid sequence of SEQ ID NO: 22, or at least 99% identical to the amino acid sequence of SEQ ID NO: 22 and preferably having the same CDRs as the anti-BCMA scFv of ll1); mm0) an anti-CD70 scFv; mm1) an anti-CD70 scFv having the amino acid sequence of SEQ ID NO: 26; mm2) an anti-CD70 scFv competing with the anti-CD70 scFv of mm1) for specific binding to CD70;mm3) an anti-CD70 scFv having the same CDRs as the anti-CD70 scFv of mm1); andmm4) an anti-CD70 scFv having an amino acid sequence at least 85% identical to the aminoacid sequence of SEQ ID NO: 26, at least 90% identical to the amino acid sequence of SEQ ID NO: 26, at least 95% identical to the amino acid sequence of SEQ ID NO: 26, at least 98% identical to the amino acid sequence of SEQ ID NO: 26, or at least 99% identical to the amino acid sequence of SEQ ID NO: 26 and preferably having the same CDRs as the anti-CD70 scFv of mm1); nn1) an anti-CD70 scFv having the amino acid sequence of SEQ ID NO: 27; nn2) an anti-CD70 scFv competing with the anti-CD70 scFv of nn1) for specific binding to CD70;nn3) an anti-CD70 scFv having the same CDRs as the anti-CD70 scFv of nn1); andnn4) an anti-CD70 scFv having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 27, at least 90% identical to the amino acid sequence of SEQ ID NO: 27, at least 95% identical to the amino acid sequence of SEQ ID NO: 27, at least 98% identical to the amino acid sequence of SEQ ID NO: 27, or at least 99% identical to the amino acid sequence of SEQ ID NO: 27 and preferably having the same CDRs as the anti-CD70 scFv of nn1); oo1) a Baff receptor-binding scBaff (single-chain Baff) comprising three protomers of Baff connected by peptide linkers, wherein the scBaff (single-chain Baff) is identical to the amino acid sequence of SEQ ID NO: 28 or has an amino acid sequence at least 85% identical to the amino acid sequence of SEQ ID NO: 28, at least 90% identical to the amino acid sequence of SEQ IDNO: 28, at least 95% identical to the amino acid sequence of SEQ ID NO: 28, at least 98% identical to the amino acid sequence of SEQ ID NO: 28, or at least 99% identical to the amino acid sequence of SEQ ID NO: 28; pp1) a TNFR2-binding scTNF80 (single-chain TNF80) comprising three protomers of TNF80, a mutant of TNF with two mutations preventing binding to TNFR1 thus ensuring specific TNFR2 binding, connected by peptide linkers, wherein the scTNF80 (single-chain TNF80) is identical to the amino acid sequence of SEQ ID NO: 37 or has an amino acid sequence at least 85% identical to the amino acid sequence of SEQ ID NO: 37, at least 90% identical to the amino acid sequence of SEQ ID NO: 37, at least 95% identical to the amino acid sequence of SEQ ID NO: 37, at least 98% identical to the amino acid sequence of SEQ ID NO: 37, or at least 99% identical to the amino acid sequence of SEQ ID NO: 37;qq0) an anti-CD38 VHH;qq1) an anti-CD38 VHH having the amino acid sequence of SEQ ID NO: 43; qq2) an anti-CD38 VHH competing with the anti-CD38 VHH of qq1) for specific binding to CD38;qq3) an anti-CD38 VHH having the same CDRs as the anti-CD38 VHH of qq1); andqq4) an anti-CD38 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 43, at least 90% identical to the amino acid sequence of SEQ ID NO: 43, at least 95% identical to the amino acid sequence of SEQ ID NO: 43, at least 98% identical to the amino acid sequence of SEQ ID NO: 43, or at least 99% identical to the amino acid sequence of SEQ ID NO: 43 and preferably having the same CDRs as the anti-CD38 VHH of qq1);rr1) an anti-CD38 VHH having the amino acid sequence of SEQ ID NO: 44;rr2) an anti-CD38 VHH competing with the anti-CD38 VHH of rr1) for specific binding to CD38;rr3) an anti-CD38 VHH having the same CDRs as the anti-CD38 VHH of rr1); andrr4) an anti-CD38 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 44, at least 90% identical to the amino acid sequence of SEQ ID NO: 44, at least 95% identical to the amino acid sequence of SEQ ID NO: 44, at least 98% identical to the amino acid sequence of SEQ ID NO: 44, or at least 99% identical to the amino acid sequence of SEQ ID NO: 44 and preferably having the same CDRs as the anti-CD38 VHH of rr1);ss0) an anti-CD25 VHH;ss1) an anti-CD25 VHH which does not block IL-2 binding;ss2) an anti-CD25 VHH blocking IL-2 binding;ss3) an anti-CD25 VHH having the amino acid sequence of SEQ ID NO: 45; ss4) an anti-CD25 VHH competing with the anti-CD25 VHH of ss3) for specific binding to CD25;ss5) an anti-CD25 VHH having the same CDRs as the anti-CD25 VHH of ss3); andss6) an anti-CD25 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 45, at least 90% identical to the amino acid sequence of SEQ ID NO: 45, at least 95% identical to the amino acid sequence of SEQ ID NO: 45, at least 98% identical to the amino acid sequence of SEQ ID NO: 45, or at least 99% identical to the amino acid sequence of SEQ ID NO: 45 and preferably having the same CDRs as the anti-CD25 VHH of ss3); tt1) an anti-CD25 VHH having the amino acid sequence of SEQ ID NO: 46; tt2) an anti-CD25 VHH competing with the anti-CD25 VHH of tt1) for specific binding to CD25;tt3) an anti-CD25 VHH having the same CDRs as the anti-CD25 VHH of tt1); andtt4) an anti-CD25 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 46, at least 90% identical to the amino acid sequence of SEQ ID NO: 46, at least 95% identical to the amino acid sequence of SEQ ID NO: 46, at least 98% identical to the amino acid sequence of SEQ ID NO: 46, or at least 99% identical to the amino acid sequence of SEQ ID NO: 46 and preferably having the same CDRs as the anti-CD25 VHH of tt1);uu0) an anti-CD30 VHH;uu1) an anti-CD30 VHH having the amino acid sequence of SEQ ID NO: 48; uu2) an anti-CD30 VHH competing with the anti-CD30 VHH of uu1) for specific binding to CD30;uu3) an anti-CD30 VHH having the same CDRs as the anti-CD30 VHH of uu1); anduu4) an anti-CD30 VHH having an amino acid sequence at least 85% identical to the amino acidsequence of SEQ ID NO: 48, at least 90% identical to the amino acid sequence of SEQ ID NO: 48, at least 95% identical to the amino acid sequence of SEQ ID NO: 48, at least 98% identical to the amino acid sequence of SEQ ID NO: 48, or at least 99% identical to the amino acid sequence of SEQ ID NO: 48 and preferably having the same CDRs as the anti-CD30 VHH of uu1); vv1) IL2; vv2) an IL2 mutant; and vv3) an IL2 having the amino acid sequence of SEQ ID NO: 47; and ww1) any one or more of the domains as defined in claim 29, or any one or more of the domains according to d0), d1), d2), d3, d4), e1), e2), e3), e4), f1), f2), f3), f4), g0), g1), g2), g3), g4), k0), k1), k2), k3), k4), l0), l1), l2), l3), l4), m1), m2), m3), m4), s1), s2), s3), or s4) as defined in claim 29.

31. The fusion protein construct according to any one of the preceding claims, wherein the fusionprotein construct does not comprise more than two scFv fragments.

32. The fusion protein construct according to any one of the preceding claims, wherein the fusionprotein construct does not comprise more than one scFv fragment.

33. The fusion protein construct according to any one of the preceding claims, wherein the fusionprotein construct does not comprise any scFv fragment.

34. The fusion protein construct according to any one of the preceding claims, wherein each of theN-termini of the scaffold domain according to i) is linked to one or more binding domains according to ii) or one or more binding domains according to iii).

35. The fusion protein construct according to any one of the preceding claims, wherein all of the oneor more binding domains according to ii) and all of the one or more binding domains according to iii) are VHH domains.

36. A pharmaceutical composition comprising a fusion protein construct according to any one of thepreceding claims.

37. A protein library comprising two or more different fusion protein constructs according to any oneof claims 1-35.

38. The protein library according to claim 37, the library comprising ten or more different fusionprotein constructs according to any one of claims 1-35.

39. A nucleic acid, or a set of nucleic acids, encoding the fusion protein construct according to anyone of claims 1-35.

40. A set of nucleic acids, encoding the protein library according to claim 37 or 38.

41. A recombinant cell containing a nucleic acid, or a set of nucleic acids, according to claim 39 andexpressing the fusion protein construct of any one of claims 1-35.

42. A method for producing a fusion protein construct according to any one of claims 1-35, themethod comprising expressing the nucleic acid or set of nucleic acids according to claim 39 in a recombinant cell according to claim 41, and harvesting the fusion protein construct.

43. A method for producing a protein library according to claim 37 or 38, the method comprisingexpressing the set of nucleic acids according to claim 40 together or separately in cells, and obtaining the protein library.

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