Conjugates of ara-AMP with lactosaminated albumin: a study on their immunogenicity in mouse and rat.
Complexes of albumin with oligosaccharides have been successfully employed in experimental chemotherapy as hepatotropic carriers of antiviral drugs or as vectors of anticancer-agents, but their clinical use is hampered by an immune response they might evoke. In the present experiments we have studied the humoral immunogenicity of conjugates of 9-beta-D-arabinofuranosyl adenine 5'-monophosphate (ara-AMP) with lactosaminated albumin (L-SA), in mice and rats. These complexes were prepared with the aim of increasing the chemotherapeutic index of ara-AMP in the treatment of chronic hepatitis B virus (HBV) infection. L-SA-ara-AMP conjugates prepared with heterologous albumin produced antibodies in mice and rats when repeatedly injected intraperitoneally. The same conjugates prepared with homologous albumin induced only low amounts of antibodies, when given by repeated intraperitoneal injection, whereas they did not evoke antibodies in mice and were tolerogenic in rats when administered repeatedly by the intravenous route. These results suggest that in a clinical use of drug conjugates prepared with oligosaccharide-albumin complexes the risk of an immune response can be reduced by employing human albumin and by injecting the conjugates by the intravenous route.
D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000276:immunology*; D001088:Arabinonucleotides / Q000276:immunology*; D005260:Female; D008297:Male; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000276:immunology*; D013045:Species Specificity; D013329:Structure-Activity Relationship; D014614:Vaccines, Synthetic / Q000276:immunology*; D001084:Vidarabine Phosphate / Q000276:immunology*
D000941:Antigens; D001088:Arabinonucleotides; D012709:Serum Albumin; D014614:Vaccines, Synthetic; C046912:lactosaminated serum albumin; D001084:Vidarabine Phosphate