Minicells defeat drug resistant cancer

Researchers led by Sydney-based biotechnology company, EnGeneIC, have reported in Nature Biotechnology that bacterially-derived minicells can be used to target previously resistant cancerous tumours, presenting the possibility of treating many patients who develop resistance to conventional chemotherapy treatments.

The minicells deliver small interfering RNA (siRNA) duplexes, which when released in tumour cells, compromise select drug resistant proteins. Further minicells can then carry a payload of cytotoxins that target the newly vulnerable tumour cells and kill them.

The potential of siRNA and short haripin RNA (shRNA) in combating cancer has been long known but the challenge has been to deliver them to the appropriate sites without them degrading before they reach their mark. The use of minicells has proven to be potential solution to this problem.

The minicells are 'empty' bacterial cells that can have their protein and RNA replaced with a selected payload, such as the siRNA. They can then be targeted via antibodies to specific tumour-cell-surface receptors to deliver their payload.

This new method could be used to treat patients who become resistant to conventional anti-cancer drug treatments, such as individuals with chronic myelogenous leukemia, a significant percentage of whom become resistant to the drug, the kinase inhibitor, imatinib mesylate, known as Glivec (Gleevec in the US), after prolongued treatment.

The new treatment was tested on mice, in which the minicells successfully inhibited the growth of drug-resistant colon, breat and uterine tumours, extending their life expectancy.

The research was conducted by Jennifer MacDiarmid and colleagues at EnGenIC along with colleagues at Cold Spring Harbor Laboratory in the US, the Victor Chang Cardiac Research Institute and the University of New South Wales, and is published in i>Nature Biotechnology.