'Trojan horse' cancer therapy beats tumours resistant to chemotherapy

Jun 28 2009

A new therapy to treat cancer has been developed by Australian scientists and it promises to have far fewer unpleasant side effects than conventional treatments and should also be much cheaper.

More importantly however is that the researchers at the Sydney-based biotechnology company EnGeneIC have come up with a 'Trojan horse' therapy which combats the resistance of tumours to chemotherapy drugs.

Currently chemotherapy treatment is used for most cancer patients and is exhausting, time-consuming and nauseating, doctors are often perplexed when the tumours they are treating develop resistance to chemotherapy drugs.

The new treatment developed by Dr Jennifer MacDiarmid and Dr Himanshu Brahmbhatt, who formed EnGenelC Pty Ltd in 2001, promises to destroy such resistant cells, potentially extending the lives of tens of thousands of patients and they say the therapy should be cheaper than conventional treatments and will have far fewer unpleasant side effects.

The 'Trojan horse' therapy uses a bacterially-derived nano-cell to penetrate and disarm the cancer cell before a second nano-cell kills it with chemotherapy drugs and 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.

They scientists say they have achieved 100% survival in mice with human cancer cells by using the 'Trojan horse' therapy in the past two years - human trials of the cell delivery system will start next week at the Peter MacCullum Cancer Centre at the Royal Melbourne Hospital and The Austin at the University of Melbourne, followed by human clinical trials planned in the coming months.

The therapy enables mini-cells called EDVs (EnGenelC Delivery Vehicle) to attach and enter the cancer cell - the initial set of mini-cells release ribonucleic acid molecules, called siRNA, which switch off the production of proteins that make the cancer cell resistant to chemotherapy - this is then followed by a second set of EDV cells which are then accepted by the cancer cell where they release chemotherapy drugs, killing off the cancer cell.

Dr MacDiarmid says that their EDVs operate as 'Trojan horses' - they arrive at the gates of the affected cells and are always allowed in and by playing the rogue cells at their own game, they switch on the gene to produce the protein to resist drugs, they then switch off the gene which, in turn, enables the drugs to enter.

One of the most exciting areas of current biotechnology research is RNA interference, or RNAi, which is designed to silence the genes responsible for producing disease-causing proteins and a number of biotechnology companies are exploring ways to manipulate RNA to block genes that produce disease-causing proteins.

Dr Brahmbhatt says treatment with conventional drug therapy causes a large number of cancer cells to die but a small percentage of the cells can produce proteins that make cancer cells resistant to chemotherapeutic drugs and as a result follow-up drug treatments can fail - when this happens tumours become untreatable and continue to flourish, ultimately killing the patient.

The new therapy allows much smaller amounts of cancer drugs to be used effectively and patients should not be in hospital for quite as long.

Dr Brahmbhatt says treatments are moving towards cancers being managed as a chronic disease rather than being regarded as a death sentence and as their treatment method does not damage the normal cells it is applicable to a wide spectrum of solid cancer types.

The scientists say the mini-cells treatments were "well tolerated with no adverse side effects or deaths in any of the actively treated animals, despite repeated dosing" - they hope that the benign nature of their EDV technology will enable cancer sufferers to carry on with their lives normally and access the therapy as out-patients.

The research is published in the current issue of Nature Biotechnology.