Microparticles Coated with Apoptotic Antigens Blunt Autoimmune Attack

The molecular processes responsible for autoimmune diseases such as multiple sclerosis (MS) can be shut down by exposing cells in the immune system to microparticles coated with antigens from cells that have been reduced to fragments by apoptosis.


Investigators at Northwestern University (Chicago, IL, USA) had previously shown that antigen-bound apoptotic cells could be injected safely into patients with MS. While this treatment induced T cell tolerance that prevented further autoimmune attack and slowed progression of the disease, it was not practical for routine clinical use. Senior author Dr. Stephen Miller, professor of immunology at Northwestern University, explained, "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. It is a costly, difficult, and time-consuming procedure."

A search for alternative methods to replace living cells as transporters of apoptotic antigens led to the development of suitable synthetic microparticles. In a paper published in the November 18, 2012, online edition of the journal Nature Biotechnology the investigators described the preparation of polystyrene or biodegradable poly(lactide-co-glycolide) microparticles coated with antigens relevant to a mouse model of MS (relapsing experimental autoimmune encephalomyelitis).

Mice with relapsing experimental autoimmune encephalomyelitis were treated by intravenous infusion of the microparticles. Results showed that treatment with the microparticles prevented the onset and modified the course of the disease. These beneficial effects required microparticle uptake by marginal zone macrophages expressing the scavenger receptor MARCO and were mediated in part by the activity of regulatory T cells, abortive T-cell activation, and T-cell anergy.

The biodegradable poly(lactide-co-glycolide) used to formulate the microparticles has already been approved by the [US] Food and Drug Administration and is currently used in sutures as well as in clinical trials to deliver anticancer agents. Dr. Miller said, "I think we have come up with a very potent way to induce tolerance that can be easily translated into clinical practice. We are doing everything we can now to take this forward."

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