Fiume L, Busi C, Preti P, Spinosa G
Dipartimento di Patologia Sperimentale, Bologna, Italy.
Cancer Drug Deliv. 1987;4(3):145-50. doi: 10.1089/cdd.1987.4.145.
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.
白蛋白与寡糖的复合物已成功应用于实验性化疗，作为抗病毒药物的亲肝载体或抗癌剂的载体，但其临床应用受到可能引发的免疫反应的阻碍。在本实验中，我们研究了9-β-D-阿拉伯呋喃糖基腺嘌呤5'-单磷酸酯（ara-AMP）与乳糖胺化白蛋白（L-SA）的缀合物在小鼠和大鼠中的体液免疫原性。制备这些复合物的目的是提高ara-AMP治疗慢性乙型肝炎病毒（HBV）感染的化疗指数。用异源白蛋白制备的L-SA-ara-AMP缀合物经腹腔反复注射后，在小鼠和大鼠中产生了抗体。用同源白蛋白制备的相同缀合物经腹腔反复注射时，仅诱导产生少量抗体，而经静脉反复给药时，它们在小鼠中未引发抗体，在大鼠中具有耐受性。这些结果表明，在临床使用由寡糖-白蛋白复合物制备的药物缀合物时，通过使用人白蛋白并通过静脉途径注射缀合物，可以降低免疫反应的风险。
