Tumor-specific novel taxoid-monoclonal antibody conjugates

  • J Med Chem. 2002 Dec 19;45(26):5620-3. doi: 10.1021/jm025540g.
Iwao Ojima  1 ,  Xudong Geng ,  Xinyuan Wu ,  Chuanxing Qu ,  Christopher P Borella ,  Hongsheng Xie ,  Sharon D Wilhelm ,  Barbara A Leece ,  Laura M Bartle ,  Victor S Goldmacher ,  Ravi V J Chari
Affiliations
  • 1. Department of Chemistry, State University of New York at Stony Brook, Stony Brook, New York 11794-3400, USA. [email protected]
PMID: 12477344 DOI: 10.1021/jm025540g
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.