title: In vitro and in vivo comparison of a randomly coupled antibody fragment-enzyme conjugate with a site-specific conjugate.
abstract: Two antibody fragment-enzyme conjugates, one obtained by random coupling of the two protein component, the other by site-specific ligation of the same component, were compared in vitro and in vivo for their usefulness in antibody directed enzyme prodrug therapy (ADEPT). The in vitro studies have shown that the site-specific conjugate has a higher antigen binding capacity, while both conjugates had similar specific enzymic activities. In vivo, the site-specific conjugate was cleared more rapidly. When correction was made for this faster clearance, both conjugates showed similar antitumor efficacy in a mouse xenograft system upon administration of a prodrug.
authors.affiliation: Département de Biochimie Médicale, C.M.U., Geneva, Switzerland.
authors.forename: R C
authors.initials: RC
authors.lastname: Werlen
authors.forename: R E
authors.initials: RE
authors.lastname: Offord
authors.forename: D C
authors.initials: DC
authors.lastname: Blakey
authors.forename: S J
authors.initials: SJ
authors.lastname: East
authors.forename: R G
authors.initials: RG
authors.lastname: Melton
authors.forename: K
authors.initials: K
authors.lastname: Rose
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D007128:Immunoglobulin Fragments / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D066298:In Vitro Techniques; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011355:Prodrugs / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D015431:Weight Loss / Q000187:drug effects; D011623:gamma-Glutamyl Hydrolase / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D018796:Immunoconjugates; D007128:Immunoglobulin Fragments; D011355:Prodrugs; D011623:gamma-Glutamyl Hydrolase