title: Tumor-specific novel taxoid-monoclonal antibody conjugates.
abstract: Taxoids bearing methyldisulfanyl(alkanoyl) groups for taxoid-antibody immunoconjugates were designed, synthesized and their activities evaluated. A highly cytotoxic C-10 methyldisulfanylpropanoyl taxoid was conjugated to monoclonal antibodies recognizing the epidermal growth factor receptor (EGFR) expressed in human squamous cancers. These conjugates were shown to possess remarkable target-specific antitumor activity in vivo against EGFR-expressing A431 tumor xenografts in severe combined immune deficiency mice, resulting in complete inhibition of tumor growth in all the treated mice.
authors.affiliation: Department of Chemistry, State University of New York at Stony Brook, Stony Brook, New York 11794-3400, USA. iojima@notes.cc.sunysb.edu
authors.forename: Iwao
authors.initials: I
authors.lastname: Ojima
authors.forename: Xudong
authors.initials: X
authors.lastname: Geng
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Wu
authors.forename: Chuanxing
authors.initials: C
authors.lastname: Qu
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Borella
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Xie
authors.forename: Sharon D
authors.initials: SD
authors.lastname: Wilhelm
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Leece
authors.forename: Laura M
authors.initials: LM
authors.lastname: Bartle
authors.forename: Victor S
authors.initials: VS
authors.lastname: Goldmacher
authors.forename: Ravi V J
authors.initials: RV
authors.lastname: Chari
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066246:ErbB Receptors / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D016513:Mice, SCID; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000737:chemistry*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018796:Immunoconjugates; D011355:Prodrugs; D066246:ErbB Receptors; D017239:Paclitaxel