Monomeric recombinant molecules prove generally unsatisfactory for in vivo use. Most biological systems are multivalent either structurally, associating different chains, or functionally, when crosslinked by their ligands. Mimicking natural molecules for immune intervention implies the need for multimerizing systems to create multivalent molecules capable of interfering with physiological processing. A multivalent anti-Rh(D) recombinant protein has been designed by reconstructing the antibody binding site of a human monoclonal antiRh(D) antibody as a single-chain-Fv mini-antibody, then multimerizing it by inserting at its C-terminal end the C-terminal part of the C4 binding protein (C4bp) alpha chain, responsible for the octamcr multimerization of that molecule. This study confirmed that the C-terminal part of the alpha chain of C4bp is sufficient to induce polymerization during protein synthesis, and, though the expression vector codes only for monomers, that multimcrs are assembled in the cell without necessity for secondary modifications. This soluble multivalent recombinant molecule was functional, bound Rh(D| positive red blood cells and agglutinated them in a specific fashion and did not activate complement. It will be possible to construct hetcromultimcrs associating antibody sites of different specificities or antibody sites with molecules bearing other functions. This demonstration model opens the way for future in vivo use of multivalent molecules associating antibody valences and other functional molecules for cell targeting, imaging or removal of cells such as Rh(D) positive erythrocytes for preventing Rh alloimmunization.
|Number of pages||1|
|Publication status||Published - 1997|