| abstract |
A conjugate comprising a bacterial superantigen and an antibody residue, wherein the superantigen is staphylococcal enterotoxin E (SEE), in which the amino acid sequence of the superantigen comprises regions A to E, in which region A is within the TCR binding site and determines TCR binding, and regions B to E determine binding to MHC class II molecules, into which the following amino acid residue replacements have been introduced within region C : K79E, K81E, K83S, K84S, and in which the following amino acid residue replacements have been introduced within region A: R20G, N21T, S24G, R27K, and in which optionally also amino acids at position 173 and / or position 204 within region A has / has been replaced, and in which substitution D227S (or A) has been introduced within region E, and in which one or more of the remnants of amino acids at positions 34, 35, 39, 40, 41 , 42, 44, 45 and 49 within region B and / or at positions 74, 75, 78 within region C and / or positions 187, 188, 189, 190 within region D and / or in the position and / or positions 217, 220, 222, 223, 225 within region E, so that the substituted superantigen has a reduced seroreactivity compared to that of the superantigen from which it derives, and in which the rest of antibody is a full-length antibody or any other active antigen-binding antibody fragment, which is directed against a cell surface structure associated with cancer. |