Possible consequences of human antibody responses on the biodistribution of fragments of human, humanized or chimeric monoclonal antibodies: a note of caution.
The effect of anti-combining site antibody responses on the biodistribution of monoclonal antibodies intended for diagnostic or therapeutic purposes is considered. The new generation of chimeric, humanized or human antibodies may well still be immunogenic in man, due to reaction against their combining sites. The likely consequence of this immunogenicity is clearance of antibodies from the circulation. This is already appreciated, and can be modelled in animal studies. However the effect of such anti-combining site responses on the biodistribution of F(ab')2 or Fab fragments of chimeric or human antibodies, or the new generation of fragments such as Fv, is a yet unknown. Animal modelling studies suggest that anti-combining site responses may have totally unexpected consequences. They may not lead to clearance of fragments. Indeed survival of fragments can be greatly prolonged, but target recognition prevented.
Pimm
M V
MV
Cancer Research Laboratories, University of Nottingham, U.K.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D000917:Antibody Formation / Q000502:physiology*; D006801:Humans; D007128:Immunoglobulin Fragments / Q000378:metabolism*; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007128:Immunoglobulin Fragments; D011993:Recombinant Fusion Proteins