Cancer cells have a natural 'rehoming' ability whereby circulating cancer cells can migrate back to the main tumour. Researchers at the Brigham and Women's Hospital (BWH) in Massachusetts used genome editing on cancer cells to make them lethal to other tumour cells, and allowed the rehoming behaviour to deliver the killer cells to the tumour site.
'With our technique, we show it is possible to reverse-engineer a patient's own cancer cells and use them to treat cancer,' said author Dr Khalid Shah director of the Centre for Stem Cell Therapeutics and Imaging in the BWH Department of Neurosurgery at Harvard Medical School. 'We think this has many implications and could be applicable across all cancer cell types.'
Dr Shah's team used CRISPR/Cas9 genome-editing on cancer cells, making them express a protein called S-TRAIL which initiates cell death in many kinds of tumour cells. The edited cells were then introduced into the mice and the rehoming mechanism carried them to the tumour sites.
The edited cells also contained a kill-switch, meaning that they were designed to be easily eliminated by a drug after they killed other tumour cells. This is to prevent the edited cells from proliferating and causing further tumours.
The researchers tested the therapy in mice who had primary and recurrent brain cancer, and in mice with breast cancer that had spread to the brain. The tumours were reduced in the mice that received the edited cells, and these mice survived for longer than their untreated counterparts.
Two different versions of the treatment were studied – one used cells from the tumour of the mouse subject, which were removed, edited and then re-introduced. The other approach used pre-engineered cells from another individual which were HLA-matched to the recipient.
Both approaches were successful and have potential for cancer treatment in humans: using the patient's own cells is slower, but the risk of rejection or immune response with this method is much lower.