Queensland researchers have conducted Australia's first clinical trial using genetically engineered immune cells to make bone marrow transplantation for blood cancer safer.
The results of the phase I clinical trial have been published today in the journal Clinical Cancer Research.
The research was led by QIMR Berghofer scientist Dr Siok Tey. Dr Tey is also a bone marrow transplant physician at the Royal Brisbane and Women's Hospital where the trial occurred.
About 10,000 Australians are diagnosed with blood cancers such as leukaemia and lymphoma each year.
Bone marrow transplantation is the only chance of a cure for patients with high-risk forms of blood cancer, Dr Tey said, with about 700 Australians undergoing a bone marrow transplant each year.
"However, there are many others who need a transplant but cannot undergo one because they do not have a suitably matched donor," she said.
"The key to bone marrow transplantation is the immune cells. Immune cells are a double-edged sword – they are necessary for fighting cancer and infection but they can also cause unwanted tissue damage, known as graft-versus-host disease.
"This is why we generally need to use fully-matched donors. In this clinical trial, for the first time in Australia, we used genetic engineering to make transplantation safer so we could use donors who were only partially matched.
"We take the immune cells from the partially matched donors, then we insert a gene into these cells which enables the cells to be killed off if they cause complications, such as graft-versus-host disease."
Dr Tey said the genetic engineering was performed at QIMR Berghofer's cell manufacturing facility, Q-Gen Cell Therapeutics and patients received the immune cells after their bone marrow transplant at the RBWH.
"What we found really amazing was that these immune cells can massively grow in number in the patients," she said.
"We were able to show, using two independent molecular techniques that a single genetically modified immune cell, when challenged by a cancer, could split into millions and millions of cells within a few days.
"This immense capacity for rapid expansion was something that had not been shown before and really demonstrates the 'power of one': One cell, if it is the right cell, can grow rapidly and help control cancer or infection."
Anthony Takken was 53 years old when he was diagnosed with high-risk acute myeloid leukaemia in 2014.
His only chance for a cure was a bone marrow transplant but he did not have a fully matched donor.
He has siblings but none of them was a full match because even brothers and sisters have only a one in four chance of being a full match.
Anthony became the first person to go on the clinical trial in January 2015.
Dr Tey and her team took immune cells from his brother, who was a partial match, and genetically modified them.
Mr Takken then underwent a bone marrow transplant from the same brother, and three weeks later had an infusion of the gene-modified cells.
"My cancer has now been in remission for 3.5 years. I have a few health challenges but I have returned to work, I'm travelling the world and the doctors say that the chances of the leukaemia coming back are very low," Mr Takken said.
"At the time I was diagnosed, I was faced with leaving my 16 and 17 old sons to grow up without a father. Thanks to the gene therapy trial, I've now made it 3.5 years past my original expiry date!
"I'm grateful that Queensland is a significant hub in the world for this kind of research and treatment and I hope it can continue to be well funded because it gives people like me a chance of surviving and living and contributing to society."
Dr Tey said although it was a small clinical trial, it was critical in demonstrating the ability of even a single cell, to control cancer and infection.
"Cancer immunotherapy is one of the most exciting developments in cancer treatment this decade. Bone marrow transplantation is actually the earliest form of cancer immunotherapy and continues to be a very effective form of treatment," she said.
"Our trial gives hope to all the people who haven't been able to find a suitable bone marrow donor in the past.
"Every day we are working hard to find the next line of treatment for people with leukemia, people needing a transplant and treating complications from transplant.
"It's exciting that this huge technological development is happening here in Queensland, at QIMR Berghofer and the RBWH. It is also exciting that this study paves the way for the use of other gene-engineering technology that has supercharged the cancer immunotherapy field in the past five to 10 years.
"We are now working on our next generation of clinical trials to use gene-modified cells to fight blood cancer and treat complications of bone marrow transplantation."
