Fagnani R, Hagan M S, Bartholomew R
Hybritech Incorporated, San Diego, California 92126.
Cancer Res. 1990 Jun 15;50(12):3638-45.
This communication describes the covalent modification of monoclonal and polyclonal antibodies with oxidized dextrans of low molecular weight to generate conjugates having low immunogenicity in vivo. Conjugation conditions were optimized to generate monomeric, dextran-modified antibodies, free of both high-molecular-weight polymeric aggregates and unmodified antibodies. Conjugates could be prepared with varying levels of dextran substitution. These conjugates retained optimal immunoreactivity as well as in vivo pharmacokinetics and tumor-localization properties. In addition, multiple i.v. administrations of dextran-modified antibodies in animals did not elicit a measurable immune response to either the antibody or the dextran portion of these conjugates.
本通讯描述了用低分子量氧化葡聚糖对单克隆抗体和多克隆抗体进行共价修饰，以生成在体内具有低免疫原性的缀合物。优化了缀合条件，以生成无高分子量聚合物聚集体和未修饰抗体的单体葡聚糖修饰抗体。可以制备具有不同葡聚糖取代水平的缀合物。这些缀合物保留了最佳的免疫反应性以及体内药代动力学和肿瘤定位特性。此外，在动物中多次静脉注射葡聚糖修饰的抗体不会引发对这些缀合物的抗体或葡聚糖部分的可测量免疫反应。
