【路透社】Scientists kill cancer cells with "trojan horse"

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Scientists kill cancer cells with "trojan horse"
http://www.reuters.com/article/topNews/idUSTRE55R1Q320090629
Mon Jun 29, 2009 5:57am EDT    By Michael Perry






Australian scientists have developed a "trojan horse" therapy to combat cancer, using a bacterially-derived nano cell to penetrate and disarm the cancer cell before a second nano cell kills it with chemotherapy drugs.


The "trojan horse" therapy has the potential to directly target cancer cells with chemotherapy, rather than the current treatment that sees chemotherapy drugs injected into a cancer patient and attacking both cancer and healthy cells.


Sydney scientists Dr Jennifer MacDiarmid and Dr Himanshu Brahmbhatt, who formed EnGenelC Pty Ltd in 2001, said they had achieved 100 percent survival in mice with human cancer cells by using the "trojan horse" therapy in the past two years.


The scientists plan to start human clinical trials in the coming months. Human trials of the cell delivery system will start next week at the Peter MacCullum Cancer Center at the Royal Melbourne Hospital and The Austin at the University of Melbourne.


The therapy, published in the latest Nature Biotechnology journal, sees mini-cells called EDVs (EnGenelC Delivery Vehicle) attach and enter the cancer cell.


The first wave of mini-cells release ribonucleic acid molecules, called siRNA, which switch off the production of proteins that make the cancer cell resistant to chemotherapy.


A second wave of EDV cells is then accepted by the cancer cell and releases chemotherapy drugs, killing the cancer cell.


"The beauty is that our EDVs operate like 'Trojan Horses' They arrive at the gates of the affected cells and are always allowed in," said MacDiarmid.


"We are playing the rogue cells at their own game. They switch-on the gene to produce the protein to resist drugs, and we are switching-off the gene which, in turn, enables the drugs to enter."


DISARMING TUMOUR CELLS


RNA interference, or RNAi, is designed to silence genes responsible for producing disease-causing proteins and is one of the hottest areas of biotechnology research. RNA was the basis of the 2006 Nobel Prize in medicine.


Dozens of biotechnology companies are looking for ways to manipulate RNA to block genes that produce disease-causing proteins involved in cancer, blindness or AIDS.


Brahmbhatt said that after treatment with conventional drug therapy, a large number of cancer cells die but a small percentage of the cells can produce proteins that make cancer cells resistant to chemotherapeutic drugs.


"Consequently, follow-up drug treatments can fail. The tumors thus become untreatable and continue to flourish, ultimately killing the patient," said Brahmbhatt.


"We want to be part of moving toward a time when cancers can be managed as a chronic disease rather than being regarded as a death sentence," he said.

The Nature report said the mini-cells were "well tolerated with no adverse side effects or deaths in any of the actively treated animals, despite repeated dosing."


"Significantly, our methodology does not damage the normal cells and is applicable to a wide spectrum of solid cancer types," said MacDiarmid.


"The hope is that the benign nature of this EDV technology should enable cancer sufferers to get on with their lives and operate normally using out-patient therapy."