Modified transferin-antibody fusion proteins

[0392] A trans-body comprising a transferrin molecule and a single chain antibody can be produced. A specific example of a SCA that can be fused to transferrin is anti-TNF (tumor necrosis factor). Anti-TNF has been used to treat various inflammatory and autoimmune diseases such as rheumatoid arthritis. TNF-SCA could be fused to the N- or C-terminus of modified transferrin in such manner that the coding N-terminus of TNF-SCA is directly attached to the C-terminal amino acid of Transferrin or the C-terminal amino acid of TNF-SCA is directly attached to the N-terminal amino acid of Transferrin. Alternatively, a peptide linker could be inserted to provide more separation between Transferrin and TNF-SCA and allow more spatial mobility to the two fused proteins. Several examples of TNF-SCA are shown in FIG. 4A-4B.

[0393] A fusion protein between modified Tf (mTf) and TNF-SCA is made by fusing one or more copies of the nucleotide sequence encoding the SCA to the nucleotide sequence of Tf to p

[0403] A trans-body comprising transferrin and CDRs may be generated. These usually consist of relatively short stretches of peptides. Antibodies normally have three CDRs in their heavy chains and three in their light chains. One or more CDRs of an antibody which can interact with the antigen can be fused to modified transferrin to confer antigen binding activity on the transferrin molecule. The CDRs can be fused to the N-, C-, N- and C-termini or engineered into the interior scaffold of transferrin. Examples of the CDR sequences from anti-TNF antibodies are shown in the TNF-SCA FIGS. 4A-4B. cDNAs corresponding to one or more CDRs can be fused with modified transferrin to confer TNF binding activity to transferrin.

Insertion of CDR(s)

[0404] Examination of the N-domain of human Tf (PDB identifier 1A8E) and the full Tf model AAAaoTfwo, generated using the ExPasy Swiss Model Server with the rabbit model 1JNF as template, reveals a number of potential sites for insertion of a peptide, ei

[0410] The trans-bodies in Examples 1 and 2 can be further modified to include an antigenic or immunomodulatory peptide. The desired peptide can be inserted in the transferrin portion of the trans-body. In this way, the modified trans-body not only can bind their antigens, but can also induce an immune response in the host.