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.
Safavy
Ahmad
A
Division of Radiation Biology, Department of Radiation Oncology and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA.
Raisch
Kevin P
KP
D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry* / Q000276:immunology* / Q000302:isolation & purification; D007167:Immunotherapy; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology; D017239:Paclitaxel / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D019802:Succinic Acid
D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D019802:Succinic Acid; D066246:ErbB Receptors; D017239:Paclitaxel