Tumor-specific novel taxoid-monoclonal antibody conjugates.
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.
Ojima
Iwao
I
Department of Chemistry, State University of New York at Stony Brook, Stony Brook, New York 11794-3400, USA. iojima@notes.cc.sunysb.edu
Geng
Xudong
X
Wu
Xinyuan
X
Qu
Chuanxing
C
Borella
Christopher P
CP
Xie
Hongsheng
H
Wilhelm
Sharon D
SD
Leece
Barbara A
BA
Bartle
Laura M
LM
Goldmacher
Victor S
VS
Chari
Ravi V J
RV
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
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018796:Immunoconjugates; D011355:Prodrugs; D066246:ErbB Receptors; D017239:Paclitaxel