A new way of delivering oncology drugs to tumours, using "mini cells" derived from bacteria, has been clinically tested for the first time and found to be safe, well-tolerated and even induced stable disease in patients with advanced, incurable cancers with no treatment options remaining. The research, which was presented at the 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, held from 6th to 9th November, in Dublin, Ireland, suggested 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.
Drs Himanshu Brahmbhatt and Jennifer MacDiarmid, the founders of EnGeneIC, a Sydney, Australia-based biotechnology company, designed the mini cells to deliver oncology drugs directly to tumour cells, thereby reducing the toxic side effects that are seen when chemotherapy is given to patients systemically. The mini cells are created from small bubbles of cell membrane from the surface of mutant bacteria. The mini cells can then be loaded with chemicals, such as oncology drugs, and coated with antibodies that home in on receptors on the surface of tumour cells. The mini cells target the cancer cells, while avoiding normal cells that do not have the same receptors. The cancer cell recognises the bacteria from which the mini cell has been derived and activates its standard defence by swallowing the mini cell, which exposes the cell nucleus to whatever oncology drug the mini cell is carrying.
Each mini cell is around 200 times smaller in diameter than a human hair, measuring approximately 400nm. Nonetheless, this is much larger than synthetic particles in development for drug delivery. This larger size means that the mini cells preferentially fall out of the leaky blood vessels around the tumour and are not carried to the liver, gastro-intestinal tract and skin where they could cause adverse side effects, like smaller particles can.
In the EORTC-NCI-AACR-presented study, the researchers loaded the cells with paclitaxel and coated the mini cells with an antibody targeting them to tumours expressing the epidermal growth factor receptor, a protein that is found on the surface of many cancer cells. The study was then conducted in the way standard Phase I studies are conducted to determine the safety and toxicity of mini cells by treating small groups of patients with progressively higher doses of mini cells, and closely monitoring safety and toxicity. A total of 28 patients with advanced, incurable cancers were treated with the mini cells in four centres in Australia. Ten patients had stable disease at six weeks and received more than one cycle of mini cells.
The key finding of the study was that mini cells can be given safely to patients with advanced cancer. Additionally, the researchers showed that multiple doses could be administered, with one patient receiving 45 doses over 15 months. The major toxicity 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 the team found that there were additional side effects, in particular changes in liver function tests, which, although asymptomatic, prevented raising the doses of the treatment higher.
Phase II trials of the mini cells are now being planned, including a trial in patients with glioblastoma using mini cells loaded with doxorubicin. The researchers also aim to develop imaging methods to track the mini cells in patients.