A new way of controlling the immune system's 'natural killer' cells has been identified, which could help prevent rejection of transplanted cells.
Natural killer cells act as a front-line defence against foreign cells in the body. Overcoming this defence has represented a major challenge to transplant, cancer immunotherapy and regenerative medicine. The new research provides a possibility to disguise transplanted cells so that they are 'invisible' to this immune defence.
'As a cardiac surgeon, I would love to put myself out of business by being able to implant healthy cardiac cells to repair heart disease', said the study's lead author Professor Tobias Deuse, from the Department of Surgery at University of California, San Francisco. 'And there are tremendous hopes to one day have the ability to implant insulin-producing cells in patients with diabetes or to inject cancer patients with immune cells engineered to seek and destroy tumours. The major obstacle is how to do this in a way that avoids immediate rejection by the immune system'.
Professor Deuse and his colleagues genetically engineered cells to express the protein CD47 and found that these were not attacked by natural killer cells. They discovered that this was because the CD47 protein activates another protein found in the natural killer cells called SIRPα.
SIRPα was known to be important in other immune cell responses, but scientists had not previously been able to identify it in natural killer cells. 'All the literature said that natural killer cells don't have this checkpoint, but when we looked at cells from human patients in the lab we found SIRPα there, clear as day', said corresponding author Professor Sonja Schrepfer.
The team investigated whether this finding could be used to help transplanted stem cells to avoid immune rejection. To do this, they genetically engineered human cells to express rhesus monkey CD47 and transplanted these cells into monkeys. They found that the engineered cells activated the SIRPα on natural killer cells, which prevented them from being attacked.
In the future the same procedure could be performed in reverse, expressing human CD47 in pig cardiac cells, for instance, to prevent them from activating natural killer cells when transplanted into human patients.
The research team aims to create a 'hypoimmune' cell line for use in regenerative medicine that will be able to avoid immune rejection.
'Currently engineered cell therapies for cancer and fledgling forms of regenerative medicine all rely on being able to extract cells from the patient, modify them in the lab, and then put them back in the patient. This avoids rejection of foreign cells, but is extremely laborious and expensive', said Professor Schrepfer. 'Our goal in establishing a hypoimmune cell platform is to create off-the shelf products that can be used to treat disease in all patients everywhere'.
The research was recently published in the Journal of Experimental Medicine.