Probe shines light on overactive immune cells

Research may help detect, treat certain cancers, autoimmune diseases

Meet the masters of escape — cancers and many viruses that are adept at avoiding destruction by the body’s immune system.

Understanding the immunoproteasome — expressed during cell stress — may be the key to controlling this rogue behavior and could help researchers and physicians adjust immune system responses, improve anti-cancer therapies and enable drug delivery.

Darci Trader, an assistant professor of medicinal chemistry and molecular pharmacology at Purdue, has developed a probe for studying the immunoproteasome in real time. The probe can be used to study the mechanism of action and selectivity of various inhibitors and to investigate molecules that increase the activity of the immunoproteasome, opening new avenues for therapeutic treatments.

Current probes are inefficient for monitoring the activity of the immunoproteasome in live cells, because they are easily cleaved by other cellular proteases and the concentrations required can be cytotoxic to cells. 

The Purdue team’s immunoproteasome-selective probe is able to work with live cells to determine how small molecules affect the activity of the immunoproteasome and to help adjust the immune system response of people with cancers, infections and autoimmune diseases.

 “As more about the immunoproteasome is being understood, it is being validated as a potential therapeutic target. It has been found overexpressed in several different disease types, including many with little-to-no treatment options, such as pancreatic cancer and various autoimmune disorders,” Trader says.

As the probe fluoresces to indicate the activity of the immunoproteasome, the identification of small molecules could lead to increasing or decreasing activity, which can modify the signals for the immune system response. In the case of cancer or infections, the aim is a quicker immune system response. In the case of autoimmune diseases, the goal is to lessen the immune systems response.

“There is still not enough known about how or why the immunoproteasome is expressed in diseased cells. Having a tool to monitor and label immunoproteasome-expressing cells could help push the field forward and begin answering some of these questions,” Trader says.