Research Breakthrough Selectively Represses the Immune System
Autoimmune disorders occur when T-cells – a type of white blood cell within the immune system – mistake the body’s own tissues for a foreign substance and attack them. Current treatment for autoimmune disorders involves the use of immunosuppressant drugs which tamp down the overall activity of the immune system. However, these medications leave patients susceptible to infections and increase their risk of cancer as the immune system’s normal ability to identify and destroy aberrant cells within the body is compromised.
According to an article published online in Nature Biotechnology (18 November 2012), a mouse model of multiple sclerosis (MS), has been developed, using innovative technology, to selectively inhibit the part of the immune system responsible for attacking myelin. Myelin is the insulating material that encases nerve fibers and facilitates electrical communication between brain cells.
The new research takes advantage of a natural safeguard employed by the body to prevent autoreactive T-cells — which recognize and have the potential to attack the body’s healthy tissues — from becoming active. One of these natural mechanisms involves the ongoing clearance of apoptotic, or dying, cells from the body. When a cell dies, it releases chemicals that attract specific cells of the immune system called macrophages. These macrophages gobble up the dying cell and deliver it to the spleen where it presents self-antigens — tiny portions of proteins from the dying cell — to a pool of T-cells. In order to prevent autoreactive T-cells from being activated, macrophages initiate the repression of any T-cells capable of binding to the self-antigens.
One of the authors was the first to demonstrate that by coupling a specific self-antigen such as myelin to apoptotic cells, one could tap into this natural mechanism to suppress T-cells that would normally attack the myelin. The lab spent decades demonstrating that they could generate antigen-specific immune suppression in various animal models of autoimmune diseases. Recently, a preliminary clinical trial was initiated to test the safety of injecting the antigen-bound apoptotic cells into patients with MS. While the trial successfully demonstrated that the injections were safe, it also highlighted a key problem with using cells as a vehicle for antigen delivery: that is cellular therapy is extremely expensive as it needs to be carried out in a large medical center that has the capability to isolate patient’s white blood cells under sterile conditions and to re-infuse those antigen-coupled cells back into the patients. This is a costly, difficult, and time-consuming procedure.”
After trying out various formulations, the desired antigens were successfully linked to microscopic, biodegradable particles which could be taken up by circulating macrophages similar to apoptotic cells. Much to the amazement of the investigators, the antigen-bound particles were just as good, if not better, at inducing T-cell tolerance in animal models of autoimmune disorders. Then, using their myelin-bound particles, the authors were able to both prevent the initiation of MS in their mouse model as well as inhibit its progression when injected immediately following the first sign of clinical symptoms.
The research team is now hoping to begin phase I clinical trials using this new technology. The material that makes up the particles has already been approved by the FDA and is currently used in resorbable sutures as well as in clinical trials to deliver anti-cancer agents. The authors believe that the proven safety record of these particles along with their ability to be easily produced using good manufacturing practices will make it easier to translate their discovery into clinical use.