The first clinical trial involving a pioneering combination of stem cells and gene therapy for lung cancer treatment in the United Kingdom (UK) was recently announced by researchers at the University College London Hospitals (UCLH). The therapy will be tested on National Health Service (NHS) patients and has received £2 million in funding from the Medical Research Council (MRC).
The therapy is based on the use of stem cells, which are undifferentiated cells with the remarkable potential to differentiate into several different specialized cells of the body, such as cells from the skin, bone, muscle, etc. In this therapy, stem cells are used as a delivery vehicle for an effective anti-cancer gene that promotes a self-destruct pathway in malignant cells but not in healthy cells.
Preliminary data in mice has shown that this therapy can reduce and in some settings even clear tumors. The gene/cell therapy will now be primarily tested in human volunteers to determine its safety profile, and then in 56 lung cancer patients to assess its effectiveness combined with chemotherapy in comparison with the standard care employed.
“Lung cancer is very difficult to treat because the vast majority of patients are not diagnosed until the cancer has spread to other parts of the body. One therapy option for these patients is chemotherapy, but even if successful this treatment can normally only extend lives by a handful of months. Chemotherapy can also cause widespread toxic side-effects,” said the lead researcher of the trial, Dr. Sam Janes, in a news release. Lung cancer is estimated to kill approximately 34,000 people every year in the UK alone.
“We aim to improve prospects for lung cancer patients by using a highly targeted therapy using stem cells, which have an innate tendency to home in on tumors when they’re injected into the body. Once there, they switch on a ‘kill’ pathway in the cancer cells, leaving healthy surrounding cells untouched. If clinical trials are successful, our treatment could be transformative for the treatment of lung cancer, and possibly other types of tumor in future,” explained Dr. Janes.
The therapy works by altering donor stem cells making them capable of expressing an anti-cancer gene called tumor necrosis factor related apoptosis-inducing ligand (TRAIL). Once the TRAIL-carrying stem cell reaches the tumor, it triggers a signaling pathway that leads to cancer cell death.
Each patient enrolled in the trial will receive three infusions comprising a total of almost a billion cells three weeks apart. The infusion is provided one day after patients have received chemotherapy. These specific cells will be generated by a team led by Dr. Mark Lowdell at the Royal Free Hospital in London.
“Lung cancer kills more men and women than any other cancer and improving the outcome for patients with this terrible disease is one of the biggest challenges we face. This new therapy, which uses modified stem cells to target the tumor directly is truly at the cutting edge and will draw on the UK’s unique position as a leader in the field of cell-based therapies,” concluded Dr. Chris Watkins, the MRC’s Director of Translational Research and Industry.