abstract |
An antigen-binding molecule containing a TNF family ligand trimer comprising (a) at least one Fab molecule that can specifically bind to a target cell antigen, (b) a first and a second polypeptide that binds to each other by a disulfide bond, in which the antigen-binding molecule is characterized in that the first polypeptide contains a first heavy chain constant (CH1) or light chain constant (CL) domain and the second polypeptide contains a CL or CH1 domain, respectively, in which the second polypeptide is linked to the first polypeptide by a disulfide bond between the CH1 and CL domain, and in which the first polypeptide comprises two ectodomains of a selected member of the TNF ligand family of 4-1BBL comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 96, SEQ ID NO: 373, SEQ ID NO: 374 and SEQ ID NO: 375 or OX40L comprising the amino acid sequence of SEQ ID NO: 53 or SEQ ID NO: 54 that are connected to each other and to the CH1 or CL domain by a peptide linker and in which the second polypeptide comprises an ectodomain of said member of the TNF ligand family selected from 4-1BBL comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 96, SEQ ID NO : 373, SEQ ID NO: 374 and SEQ ID NO: 375 or OX40L comprising the amino acid sequence of SEQ ID NO: 53 or SEQ ID NO: 54 connected by means of a peptide linker to the CL or CH1 domain of said polypeptide, and further comprising (c) an Fc domain composed of a first and a second subunit that can be stably associated. |