Tweaking sugar molecules on anti-cancer antibodies improves cell-killing with fewer side effects
Antibodies engineered to carry anti-cancer drugs are increasingly being used to treat a variety of diseases, including breast cancer, but next-generation treatments could be used at lower doses and have reduced side effects.
Using biochemical techniques, researchers at the University of Oxford have shown that destruction of cancer cells can be enhanced by optimising trastuzumab antibodies (trade name Herceptin), used to treat HER2+ breast and stomach cancers, while reducing dose and side effects.
Dr. Weston Struwe, one of the co-authors of the study, and his colleagues used the sugars normally present on trastuzumab antibodies as a scaffold for adding anti-cancer drugs. In doing so they could modulate the amount of drug added and select for those that exhibited enhanced killing of breast cancer cells in the laboratory as well as anti-inflammatory properties, to produce a more potent treatment with reduced side effects.
By producing an antibody mixture that was more than 90% pure, they propose that this new, optimized antibody drug conjugate (ADC) would work just as well at lower doses, or better, than the current antibody treatment available clinically, meaning fewer side effects would be experienced by breast cancer patients.
“We are learning how to manipulate the function and biological impact of antibodies, such as Herceptin, by altering the sugar molecules that decorate them to optimize activity” says Dr. Struwe. “We are now exploring how the sugars could be used to attach cell-killing components to optimized antibodies and further improve their cancer-destroying capability.”
Common side effects of trastuzumab treatment include fever, nausea, fatigue, diarrhoea, and sleep issues but it can also cause more serious heart, lung or liver problems. However, trastuzumab remains one of the best treatments for most types of HER2+ cancer.
Source: PR Newswire