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RESEARCH FRONT
Contents Vol 64(6)

Cancer-targeting Antibody–Drug Conjugates: Site-specific Conjugation of Doxorubicin to Anti-EGFR 528 Fab′ through a Polyethylene Glycol Linker

Lisa P. T. Hong A , Judith A. Scoble A , Larissa Doughty A , Gregory Coia A and Charlotte C. Williams A B
+ Author Affiliations
- Author Affiliations

A CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, Vic. 3052, Australia.

B Corresponding author. Email: charlotte.williams@csiro.au




Charlotte Williams was educated at the University of Western Australia, B.Sc. (Hons), where she was awarded a Ph.D. with distinction under the supervision of Professor M. V. Baker. After postdoctoral research at The University of Oxford with Professor H. L. Anderson, she undertook a research scientist position with Johnson Matthey (U.K.) before returning to Australia and taking up a position at Starpharma Pty. Ltd. where she worked for over 5 years as a senior research chemist and research manager. Since 2009 Charlotte has held a position with CSIRO Materials Science and Engineering where she has been involved in the development of bioconjugation capabilities within the division. She is a member of both the ACS and RSC as well as an active committee member of the RACI. Her current research interests include investigations into unique and interesting methods to conjugate small molecules, peptides or proteins to larger biomolecules such as antibodies.

Australian Journal of Chemistry 64(6) 779-789 https://doi.org/10.1071/CH11071
Submitted: 12 February 2011  Accepted: 16 March 2011   Published: 27 June 2011

Abstract

Antibody–drug conjugates have been prepared to examine the effect that attaching small-molecule drugs to an antibody fragment has on antibody activity. The anticancer drug doxorubicin was covalently attached through a polyethylene glycol linker to a cancer-targeting, anti-epidermal growth factor receptor antibody fragment (Fab′). The reactivity of maleimide was compared with a substituted maleimide derivative (citraconimide) in conjugation reactions with cysteine residues on a Fab′. Introduction of polyethylene glycol increased aqueous solubility of the cytotoxic drug, which led to an improvement in overall yield of the conjugation reaction with the antibody fragment. Antibody–drug conjugates prepared retained activity of the parent antibody, as determined by antigen binding experiments measured by surface plasmon resonance.


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