A RECOMBINANT HUMAN SCFV ANTI-RH(D) ANTIBODY WITH MULTIPLE VALENCES USING A C-TERMINAL FRAGMENT OF C4-BINDING PROTEIN

Monomeric recombinant molecules prove generally unsatisfactory for in vivo use. Most biological systems are indeed multivalent either struct urally, associating different chains, or functionally, when cross-link ed by their ligands. Mimicking natural molecules for immune interventi on implies the need for multimerizing systems to create multivalent mo lecules capable of interfering with physiological processing. A multiv alent anti-Rh(D) recombinant protein has been designed by reconstructi ng the antibody binding site of a human monoclonal anti-Rh(D) antibody as a single chain Fv mini antibody, then multimerizing it by insertin g at its C-terminal end the C-terminal part of the C4 binding protein (C4bp) alpha chain, which is responsible for the octamer multimerizati on of that molecule. This soluble multivalent recombinant molecule was functional, bound red blood cells (RBCs), agglutinated them, and did not activate complement. This demonstration model opens the way for fu ture in vivo use of multivalent molecules associating antibody valence s and other functional molecules for cell targeting, imaging, or remov al of cells such as Rh(D)-positive RBCs for preventing Rh alloimmuniza tion. (C) 1997 by The American Society of Hematology.