title: A new delivery system for auristatin in STxB-drug conjugate therapy.
abstract: A key challenge in anticancer therapy is to gain control over the biodistribution of cytotoxic drugs. The most promising strategy consists in conjugating drugs to tumor-targeting carriers, thereby combining high cytotoxic activity and specific delivery. To target Gb3-positive cancer cells, we exploit the non-toxic B-subunit of Shiga toxin (STxB). Here, we have conjugated STxB to highly potent auristatin derivatives (MMA). A former linker was optimized to ensure proper drug-release upon reaching reducing environments in target cells, followed by a self-immolation step. Two conjugates were successfully obtained, and in vitro assays demonstrated the potential of this targeting system for the selective elimination of Gb3-positive tumors.
authors.affiliation: Institut Curie, CNRS, UMR 3666/INSERM U1143, 26 rue d'Ulm, 75248 Cedex 05 Paris, France; Immuno Targets SAS, 116 bd du Montparnasse, 75014 Paris, France.
authors.forename: Cornélie
authors.initials: C
authors.lastname: Batisse
authors.affiliation: Institut Curie, CNRS, UMR 3666/INSERM U1143, 26 rue d'Ulm, 75248 Cedex 05 Paris, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Dransart
authors.affiliation: Institut Curie, CNRS, UMR 3666/INSERM U1143, 26 rue d'Ulm, 75248 Cedex 05 Paris, France.
authors.forename: Rafik
authors.initials: R
authors.lastname: Ait Sarkouh
authors.affiliation: Institut Curie, CNRS, UMR 3666/INSERM U1143, 26 rue d'Ulm, 75248 Cedex 05 Paris, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Brulle
authors.affiliation: Institut Curie, CNRS, UMR 3666/INSERM U1143, 26 rue d'Ulm, 75248 Cedex 05 Paris, France.
authors.forename: Siau-Kun
authors.initials: SK
authors.lastname: Bai
authors.affiliation: Immuno Targets SAS, 116 bd du Montparnasse, 75014 Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Godefroy
authors.affiliation: Institut Curie, CNRS, UMR 3666/INSERM U1143, 26 rue d'Ulm, 75248 Cedex 05 Paris, France.
authors.forename: Ludger
authors.initials: L
authors.lastname: Johannes
authors.affiliation: Institut Curie, CNRS, UMR 3666/INSERM U1143, 26 rue d'Ulm, 75248 Cedex 05 Paris, France. Electronic address: Frederic.Schmidt@curie.fr.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Schmidt
mesh_terms: D062365:Aminobenzoates / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D019073:HT29 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation; D022621:Shiga Toxin / Q000737:chemistry*
chemical_list: D062365:Aminobenzoates; D000970:Antineoplastic Agents; D004337:Drug Carriers; D009842:Oligopeptides; C543533:auristatin; D022621:Shiga Toxin
keywords: Auristatin; Cancer; Carbamate; Conjugate; Disulfide; Shiga toxin