A new type of antibody-drug conjugate (ADC) with potential for cancer therapy is described online in Nature Biotechnology. The therapy promises to be less toxic to healthy cells and could potentially have fewer nasty side-effects.
Tumour-targeted antibodies are highly efficient at recognizing cancer cells whilst ignoring normal cells and this feature has been exploited for targeted drug delivery, by attaching chemotherapy drugs to the antibodies to generate ADCs. Previous methods of making ADCs gave mixed results, with some antibodies having more drug attached than others, making it difficult to optimize dosage. William Mallet and colleagues report a new method of producing ADCs with defined amounts of drug attached. The drug is bound to the antibody in a more reproducible manner than previous ADCs and should have less negative effects on healthy cells.
The team modified specific sites in the antibody structure to facilitate drug attachment, without affecting the overall structure of the antibody or its ability to recognize cancer cells. Studies in mice showed that the new ADCs were more efficient than conventional ADCs -- achieving the same level of tumour killing with approximately half the drug dose. The new ADCs were also better tolerated by rats and monkeys, suggesting they could have fewer side-effects in humans.
William Mallet (Genentech Inc., San Francisco, CA, USA)
Jagath Reddy Junutula (Genentech Inc., San Francisco, CA, USA)
Abstract available online.
(C) Nature Biotechnology press release.
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