Research press release


Nature Biotechnology

New cancer drugs with reduced side effects


腫瘍を標的とする抗体は、非常に高い効率でがん細胞を認識する一方で、正常な細胞は無視する。標的への薬剤送達にこの性質をうまく利用しようと、化学療法薬を抗体に結合させてADCが作られてきた。これまでのADC作成法では結果はまちまちで、一部の抗体に他よりも多くの薬剤が結合してしまうために、最適な投与量を決めるのが難しかった。W Malletたちは、決まった量の薬剤を結合させてADCを作る新しい方法を編み出した。これまでのADCに比べて薬剤を抗体に再現性よく結合させるので、健康な細胞への悪い作用が少ないはずである。


A new type of antibody-drug conjugate (ADC) with potential for cancer therapy is described online this week 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.

doi: 10.1038/nbt.1480


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