Synthesis and Biological Evaluation of a Paclitaxel Immunoconjugate
Targeted cancer therapy is a promising strategy for the treatment of this disease. In this approach, a cytotoxic agent (CA), such as a drug or a radionuclide, is attached, usually covalently, to a “ targeting” vehicle (TV), which in turn is capable of recognizing specific receptor motifs on the surface of the tumor cells. Once administered systemically, the construct would localize on the tumor through the TV moiety and would release the CA cargo, resulting in the destruction of the malignant tissue. Small-molecule peptides as well as monoclonal antibodies have been used as TVs. The synthesis, antigen binding, and cytotoxicity of a covalent conjugate of the anticancer drug paclitaxel (taxol) to the anti-epidermal growth factor receptor (EGFR) monoclonal antibody C225 (IMC-C225; Erbitux®, ImClone Systems, Somerville, NJ) are described in this chapter to illustrate the methods used for the construction and in vitro evaluation of these conjugates.
Key WordsPaclitaxel, taxol C225 monoclonal antibody immunoconjugates targeted therapy drug delivery tumor targeting
- 5.Safavy, A. (2001) Taxane derivatives for targeted therapy of cancer. US patent no. 6.191.290.Google Scholar
- 20.Lloyd-Williams, P., Albericio, F., and Giralt, E. (1997) Chemical Approaches to the Synthesis of Peptides. CRC, Boca Raton, FL.Google Scholar
- 21.Siegel, M. M., Hollander, I. J., Hamann, P. R., et al. (1991) Matrix-assisted uv-laser des-orption/ionization mass spectrometric analysis of monoclonal antibodies for the determination of carbohydrate, conjugated chelator, and conjugated drug content. Anal. Chem. 63, 2470–2481.PubMedCrossRefGoogle Scholar