Mastering the microenvironment of lymph nodes.

In biology, cells typically communicate using chemical signals. These chemical signals, which are proteins or other molecules, are secreted from a cell and released into the space between cells. From there, they float over and into neighboring cells that have the appropriate receptors. 

At the University of Maryland (UMD) Fischell Department of Bioengineering (College Park, MD), Christopher Jewell, PhD, leveraged this natural process to reach and impact the microenvironment of lymph nodes, the tissues that control the body’s immune system responses. 

“We designed synthetic polymer scaffolds and loaded them with select signals,” says Dr. Jewell about the first step in this innovative process. “The signals were selected to promote immune functions – such as proliferation and memory – in T cells that are useful for combating tumors. 

The signal-filled scaffolds were inserted directly into lymph nodes and were designed to be too large to drain out of the lymph nodes. Instead, they slowly degraded, releasing the signals into lymph tissues to program anti-cancer functions in the T cells at these sites. 

“In the lymph nodes, the signals in the depots promote specialized memory T cells, “says Dr. Jewell, “and because we targeted central memory T cells, they were able to replicate at high rates and remember the specific cell targets they had been activated against for a long time. These two factors could be very useful in combating tumors and potential reoccurrences over time.” 

Exploration of this novel strategy was initially funded by Alliance for Cancer Gene Therapy. “You don’t always know the outcome of a project when you start it, obviously,” says Dr. Jewell. “When foundations like Alliance for Cancer Gene Therapy are willing to have faith and invest in concepts that others consider risky, there is potential for amazing outcomes.” 

Dr. Jewell credits this funding in helping him achieve the promising results of this study, which were published in the October 2017 issue of the Journal of Controlled Release, and for helping him launch his Jewell Laboratory at UMD. “The funding really helped us get our research lab up and running,” says Dr. Jewell. “It enabled us to secure important resources and technology that enhanced our capabilities and allowed us to advance the current project explore many future directions.” 

“What’s exciting about our lab is that it’s very multidisciplinary. We deliberately bring together the experience, skill sets and perspectives of bioengineering, immunology, chemical engineering, materials science and other scientific disciplines. This diversity is powerful. Together, we have achieved progress that might not have been realized if we’d all been working separately. We’re generating important knowledge that could one day provide new options for patients suffering from cancer and autoimmune diseases. 

“I believe gene therapy has great potential for long-lasting therapies. The idea – of engineering cells with a purpose, for example, has already permeated the mainstream. Watch any popular medical drama on TV and there’s a good chance you’ll hear talk about CAR T-cell therapy or cell engineering – if not in the show, then in the commercials! 

“Gene therapy has been embraced and will become increasingly important in coming years. The more we learn about how cells work and how information is processed at the cellular and molecular levels, the better chance we have at combatting this awful disease (cancer).”