Darrell Irvine is an engineer. But instead of designing and building airplanes, cars, or computers, Irvine engineers the immune system.
"My whole lab is devoted to figuring out how to deliver drugs and vaccines that better target the immune system," says Irvine. "We're trying to learn how to make the immune system mount more effective attacks against cancer, HIV, and other diseases." The goal is to create materials that, once in the body, can attract and be taken up by immune cells, and then spur them to seek out pathogens or tumor cells. That means fine-tuning the materials themselves, but it also requires a deep understanding of the immune processes that Irvine and his colleagues hope to stimulate. Much of Irvine's work marries materials science—particularly the development of nanoparticles—to basic immunology. Straddling the two fields is sometimes challenging, he admits. "There are almost no engineers who go to the immunology meetings," says Irvine. "And that's unfortunate, I think." To help remedy this, Irvine sends his students, who are both engineers and immunologists, to such meetings.
When he was a student, Irvine studied materials science. But he soon found himself interested in biology. As he explored various fields, immunology immediately captured his attention. "The complexity of how the immune system operates, all of these cell-cell interactions that have to happen at the right place at the right time, this enormous level of regulation—it was all just fascinating," he says.
Irvine jumped into immunology in the laboratory of Mark Davis, an HHMI investigator at Stanford University. There, Irvine solved a central question in the field. He discovered that T cells—the white blood cells that coordinate the immune system's response to threats—can respond after encountering even a single molecule isolated from an invader.
"There had been this long-standing question of just how sensitive a T cell is," says Irvine. So he devised a method to watch T cells interact with a single antigen—a small fragment of a foreign protein isolated by other immune cells. "We discovered that as a sensory organ, the immune system is just as sensitive as sight or smell. As Mark has pointed out, we know that neurons can detect a single odorant molecule and retinal cells can detect a single photon. T cells are the exact analog of that—they can detect a single molecule of a foreign antigen."
When Irvine set up his own lab at the Massachusetts Institute of Technology, he continued this work. In particular, he set about better characterizing exactly how T cells activate when they encounter other immune cells, called antigen-presenting cells (APCs). APCs are the sentinels of the immune system, collecting fragments of potentially dangerous intruders. The APCs pass these fragments to T cells, which, if they decide the fragments represent a threat, activate and begin marshaling an immune system attack.
But no one had fully characterized exactly how T cells interact with APCs. So Irvine designed a thin sheet of sticky material that captures APCs, immobilizing them so they can be monitored easily. He also developed imaging tools to watch how T cells bind with the APCs. Together, these technologies have provided an unprecedented glimpse into the interactions that drive immune system activation. Fully grasping these basics is key to boosting immunotherapies for cancer, HIV, and other diseases, Irvine says.
"My philosophy is that we can't make a technology that's really going to help against these diseases if we don't fully understand the biology that underpins the response," he says. "So we couple basic science with technology development, and that makes our lab unique."
As for technology development, Irvine spends much of his time designing nanoparticles that can boost the immune system's response to cancer and HIV. These delicately engineered particles smuggle molecular messages, such as a protein fragment, into immune cells, jump-starting the immune response to viruses or malignant cells.
"Some of what we're doing is very simple from a materials science perspective," says Irvine. "But at the same time, it has to be simple and robust to make a clinical impact. So we always walk the line between developing complex new technologies versus materials simple and robust enough to be practical for the clinic."