‘Minicells’ offer a new way to deliver anti-cancer drugs
First human tests find them to be safe and well tolerated
A new way of delivering anti-cancer drugs to tumours, using ‘minicells’ derived from bacteria, has been tested for the first time in humans and found to be safe and well tolerated.
The research, presented at the 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Dublin, Ireland, suggests that it could be possible to use this new technology for targeted delivery of other drugs to a range of cancers, and to personalise treatment by adjusting the drugs to suit the genetic make-up of each patient’s tumour.
Dr Himanshu Brahmbhatt and Dr Jennifer MacDiarmid, the founders of EnGeneIC, a biotech company in Sydney, Australia, designed the minicells, which are created from small bubbles of cell membrane pinched off the surface of mutant bacteria. The minicells can be loaded with chemicals, such as anti-cancer drugs, and coated with antibodies that home in on receptors on the surface of tumour cells. The minicells only target the cancer cells, which recognise the bacteria from which the minicell has been derived and activate their standard defence by swallowing the minicell, which exposes the cell nucleus to whatever cancer-killing drug the minicell is carrying.
Each minicell is about 200 times smaller in diameter than a human hair
Each minicell is about 200 times smaller in diameter than a human hair (400 nanometres (nM)). ‘Nonetheless, this is much larger than synthetic particles in development for drug delivery,’ said Associate Professor Benjamin Solomon, the principal investigator of the trial and a consultant medical oncologist at the Peter MaCallum Cancer Centre in Melbourne, Australia.
‘This larger size means that the minicells preferentially fall out of the leaky blood vessels around the tumour and do not end up in the liver, gut and skin where they could cause nasty side-effects like smaller particles do.’
Professor Solomon said: ‘In this study we loaded the cells with a cytotoxic chemotherapy drug called paclitaxel and coated the minicells with an antibody targeting the loaded minicells to tumours expressing the Epidermal Growth Factor Receptor (EGFR) – a protein that is found on the surface of many cancer cells.’
The research team then treated small groups of patients with progressively higher doses of minicells, closely monitoring safety and toxicity.
A total of 28 patients with advanced, incurable cancers were treated with the minicells in four centres in Australia. Ten patients had stable disease at six weeks and received more than one cycle of minicells.
The key finding of the study is that minicells can be given safely to patients with advanced cancer
‘The key finding of the study is that minicells can be given safely to patients with advanced cancer,’ said Prof Solomon.
‘Additionally, we showed that we could give multiple doses and one patient received 45 doses over 15 months. The major toxicity we observed was a mild self-limiting fever seen on the day of the infusion with little or no side effects seen in the remainder of the following week. At higher doses we found that there were additional side effects, in particular changes in liver function tests, which, although asymptomatic, prevented us from raising the doses of the treatment higher.
‘This important study shows for the first time that these bacterially-derived minicells can be given safely to patients with cancer. It thereby allows further clinical exploration of a completely new paradigm of targeted drug delivery using this platform coupled with different ‘payloads’ of cell-killing drugs or other treatments such as RNA interference, and with different targeting antibodies.’
Phase II trials of the minicells are now being planned, including a trial in patients with glioblastoma (a type of brain tumour) using minicells loaded with doxorubicin. The researchers also want to develop imaging methods to track the minicells in patients.