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Dr. Weston Struwe

Tweaking sugar molecules on anti-cancer antibodies improves cell-killing with fewer side effects

OXFORD, January 18th 2016: 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, who is funded by Oxfordshire charity Against Breast Cancer, is one of the co-authors of the study that was published in the international journal Angewandte Chemie this month.

Looking at the molecular level, Dr Struwe and 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.

For more information about Against Breast Cancer and how to get involved by volunteering or fundraising, please see the website or call 01235 534211.

Against Breast Cancer
Against Breast Cancer is a charity dedicated to funding ground-breaking research to increase survival after a breast cancer diagnosis by focusing on secondary spread, the cause of all breast-cancer related deaths. We fund research that addresses critical gaps in scientific resources and knowledge to help doctors diagnose and treat secondary breast cancer faster and more effectively, and to understand factors that may increase or reduce the risk of secondary spread so that people can make informed diet and lifestyle choices.
We have directly funded the collection of, and continue to fund the storage of over 23,000 blood and urine samples, provided annually by over 3,300 women with breast cancer from 56 hospitals across the UK in our Diet & Lifestyle Study, the largest national study of its kind. Researchers can determine differences between women who develop secondary breast cancer and those who do not by studying this collection of biological samples and dietary and lifestyle information provided at the same time.

Glycoprotein Therapeutics Laboratory
The Glycoprotein Therapeutics is based within the Oxford Glycobiology Institute at the University of Oxford. The laboratory aims to develop new therapies and vaccines by exploiting specialist knowledge and facilities in the field of glycobiology. The laboratory is led by Dr Max Crispin who has published over 60 papers and filed 4 patent applications including in the field of novel therapies for Breast Cancer. He is the co-founder of Immago Biosystems Ltd and the Against Breast Cancer Fellow at Oriel College, Oxford.
URL: http://www.bioch.ox.ac.uk/aspsite/index.asp?pageid=1040

Dr Weston Struwe

Weston recently joined the Glycoprotein Therapeutics Laboratory having worked in the Department of Chemistry in Oxford since 2012. His research exploits mass spectrometry, a technique capable of detailing the mass, size and shape of biomolecules, to understand the importance of protein glycosylation in human development, pathogenic diseases and in biotherapeutic drug design. His most recent publication demonstrated that engineering of the glycan component on the breast cancer antibody drug Herceptin, enables the addition of chemotherapeutic drugs to improve potency. Together these methods will help the group design novel antibodies with greater specificity to breast cancer cells. Weston has published over 30 papers in the field of glycobiology and mass spectrometry and is a Research Scholar at University College, Oxford.

Contact information:

Dr. Nicola Winstone, Research Manager at Against Breast Cancer
T: (+44) 01235 858289 M: (+44) 07769114403
Available to contact via mobile at any time
e.mail: nik@againstbreastcancer.org.uk
Website: www.againstbreastcancer.org.uk
Facebook: https://www.facebook.com/againstbc
Twitter: https://twitter.com/againstbc

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