Research press release


Nature Medicine

Opening the door to cancer drug delivery



J Schnitzerたちは、腫瘍の画像化とタンパク質の発現プロファイリングを行い、膜結合タンパク質アネキシンA1の切断型が、ヒトと齧歯類の腫瘍の脈管構造にあるカベオラ(輸送小胞)だけに高濃度で存在することを見いだした。そこで、この膜結合タンパク質を標的とする特異抗体を作製したところ、カベオラはこの抗体を血液中から取り込み、さらに血管壁を通過して腫瘍内部へと、濃度勾配に逆らって迅速に輸送することが分かった。

A cellular portal in rodents that enables active pumping of antibodies and other cargo from the blood into solid cancer tumors is described in a paper published online this week in Nature Medicine. This discovery opens up the possibility for new treatments and imaging strategies that can rapidly penetrate tumors at very low doses.

Overcoming drug delivery barriers has been an often-neglected area of cancer research. Despite the advent of so-called ‘smart drugs’, designed specifically to target solid tumors, the reality is that many of these drugs require high, near-toxic doses and, even then, only a small amount of the drug actually penetrates the tumor because of the dependence on passive drug delivery across blood vessels.

Using both tumor imaging and protein expression profiling, Jan Schnitzer and colleagues find that a cleaved form of the membrane binding protein annexin A1 is uniquely concentrated in the caveolae (transport vesicles) of human and rodent tumor vasculature. The authors develop a specific antibody which targets this membrane binding protein, allowing the caveolae to rapidly pump the antibody out of the blood and across the blood vessel walls into tumors, against a concentration gradient.

doi: 10.1038/nm.3623


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