Promiscuous Antibodies – targeting cancer cells
“Researchers have challenged an old immunological dogma – that an antibody can bind to only a single target or antigen – by engineering an antibody tightly to two distinct proteins.”
Germaine Fuh, along with her colleagues at Genentech, a biotechnology company in San Francisco, California, has successfully engineered the antibody that will block both a vascular endothelial growth factor (VEGF) and a human epidermal growth factor receptor 2 (HER2) [diagram is shown right] – two proteins associated with cancer. HER2 has been found to be highly expressed in aggressive breast cancers, whilst VEGF is believed to be a promoter of tumour growth.
This feat is the first of its kind, as previously no antibodies had been found or engineered that could bind both strongly and simultaneously to two substantially different antigens. Although antibodies have been found that can target multiple antigens, none have been as specific nor as strong as this Genentech-engineered antibody.
The process of engineering was quite simple, Fuh and her colleagues used an antibody for HER2 as their template, then proceeded to mutate it and screen for mutants that bound to both antigens. However, this process has been used before. In 2006, the technique was used to engineer antibodies that would bind to two similar forms of botulinum toxin. Where this case stands apart though is through the fact that Fuh’s team was able to engineer an antibody that would bind two unrelated proteins. In her own words, “This could open the door to dual-targeting types of therapy.”
The binding of the antibody to the proteins occurs on distinct, overlapping sites, and the antibody used on mice actually was able to slow tumour growth. However, the designs of the mouse models cannot be used to conclude if simultaneous targeting would be effective in fighting human cancer growth.
Advantages of this antibody:
• Treatment cost reductions (avoids multiple drug treatments)
Problems to be addressed:
• Finding the optimal dose – “How do you find the optimal does for something that binds to two targets?”
• Combination of antibodies is not always beneficial.
Fuh’s Solutions:
• “Fuh acknowledges that dosing difficulties could be a tricky to overcome, but says that the antibodies could also be engineered to bind their two targets with different efficiencies.
Harrison King – 42063957
Article: Promiscuous Antibody targets Cancer, Heidi Ledford, Nature, 19 March 2009, http://www.nature.com/news/2009/090319/full/news.2009.175.html
Picture: The two-in-one antibody, Allison Bruce and Jenny Bostrom, http://www.nature.com/news/2009/090319/full/news.2009.175.html
*All quotes taken directly from article listed above.
