Study of extracellular vesicles could enable individualized immunotherapy

LAWRENCE — Extracellular vesicles, particularly exosomes, are nanoscale sacs produced by human cells that carry critical molecular messages between cells, like biological emails.

A researcher at the University of Kansas has just earned a five-year, $1.89 million National Institutes of Health grant to investigate how 3D-biomimetic-tissue-engineered exosomes might be a new avenue for understanding long-distance, noncontact cellular communications that control our immune systems.

The grant, called the NIGMS Maximizing Investigators Research Award, is meant to boost early-stage researchers’ willingness to creatively undertake ambitious scientific projects.

Mei He, assistant professor of chemical & petroleum engineering with a joint appointment in the Department of Chemistry, and also recently named the LOC 2019 Emerging Investigator, said the grant would allow her lab to probe why “everyone has their own immune system that responds to the environment differently.”

“One simple way to explain it is some people catch a cold very easily,” she said. “But other people have much stronger immunity, and even when exposed to the same infection they know they’re not likely to catch it. That shows the individuality of the immune response from person to person, and we call it ‘immunity heterogeneity.’ Immunity heterogeneity is actually very important in cancer — one example where the immune system has completely failed and just allows the tumor cells to grow aggressively. If we can understand the immunity personality and can control it, the goal is to prime the immune system in a weak-immune-response or nonresponse cancer patient to act against the tumor. That’s the concept for precision immunotherapy.”

While researchers know that exosomes carry information so immune cells can communicate, there’s a need to understand more detail about how the system works, according to He.

“If we can see how cells write messages and how they receive messages, we can better understand the language,” He said. “When we’ve decoded it, we can put that understanding into immunity regulation.”

According to He, one of the hurdles to understanding how exosomes influence the immune system is that they’re hard to study

in vivo

, or in a living system.

“For now, we still don’t understand how immunity heterogeneity happens in an individual person,” He said. “It’s really the biggest question in the field right now and no good technology strategy so far.”

Recently, He’s lab discovered the molecular packaging of secreted exosomes changes due to the cellular culture environment as well as the surrounding community.

“The environment in a controlled lab setting is totally different than an

in vivo

biological system,” she said. “A cell structure in the lab is totally different than the cell growing in our own body. So if we want to understand a cell in our human-body system, and how they regulate, we must get exactly the right environment. But a laboratory culture won’t be able to mimic those environments. That’s really bad. You’ll try to analyze information that’s not representative of the real situation.”

To address several of the above-mentioned shortcomings, He’s five-year NIH study will focus on a few key challenges for better grasping how exosomes influence the immune system. Her research team, including the postdoc researchers and graduate students, will addresses gaps in technology by leveraging cutting-edge microfluidic technology, 3D bioprinting technology and nanotechnology. The end goal is to develop 3D, programmable biomimetic immune tissue that mimics the

in vivo

immunity microenvironment and to investigate the exosome-packaging mechanism. Eventually, the research could translate into a molecular-engineering approach to speed development of a nanodelivery and immunotherapy treatment for patients.

“The long-term goal is to advance our understanding in immunity regulation heterogeneity and eventually be able to precisely program immune responses at the molecular precision,” she said.

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