Influence of a syngeneic anti-idiotypic antibody response to a mouse anti-tumour monoclonal antibody on biodistribution of its radiolabelled Fc-intact monovalent Fab/c fragment.
It has previously been shown that a syngeneic anti-idiotypic (anti-id) antibody response generated in Balb/c mice to the monoclonal antibody (Mab) NCRC-2 can cause its clearance from the circulation. However, there was a positive prolongation of the survival of the Fab fragment, which is monovalent but also lacks Fc. The present study was carried out to examine the effect against the Fab/c fragment of this Mab, since this is also monovalent but has intact Fc. There was accelerated clearance, rather than retention. This suggests that anti-id responses prolong survival of fragments because they lack Fc, rather than only because of their monovalency. Such monovalent, Fc deficient fragments, are the type of human antibody fragments most easily obtained by genetic engineering techniques for clinical use. The present findings have implication for the effects of patients' immune responses on the biodistribution of such fragments.
Pimm
M V
MV
Cancer Research Laboratories, University of Nottingham, England.
Gribben
S J
SJ
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000912:Antibodies, Neoplasm / Q000276:immunology*; D019540:Area Under Curve; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D014018:Tissue Distribution
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D007140:Immunoglobulin Fab Fragments