Michael Mitchell, the J. Peter and Geri Skirkanich Assistant Professor of Innovation in the department of bioengineering in Penn Engineering, is one of this year’s recipients of the National Science Foundation’s CAREER Award. The award is given to early-career faculty researchers who demonstrate the potential to be role models in their field and invest in the outreach and education of their work.

Dr. Mitchell’s award will fund research on techniques for “immunoengineering” macrophages. By providing new instructions to these cells via nanoparticles laden with mRNA and DNA sequences, the immune system could be trained to target and eliminate solid tumors. The award will also support graduate students and postdoctoral fellows in his lab over the next five years.

The project aligns with Dr. Mitchell’s larger research goals and the current interest in therapies that use mRNA, thanks to the technological breakthroughs that enabled the development of COVID-19 vaccines.

“The development of the COVID vaccine using mRNA has opened doors for other cell therapies,” he said. “The high-priority area of research that we are focusing on is oncological therapies, and there are multiple applications for mRNA engineering in the fight against cancer.”

A new wave of remarkably effective cancer treatments incorporates chimeric antigen receptor T-cell (CAR-T) therapy. There, a patient’s T-cells, a type of white blood cell that fights infections, are genetically engineered to identify, target and kill individual cancer cells that accumulate in the circulatory system.

However, despite CART-T therapy’s success in treating certain blood cancers, the approach is not effective against cancers that form solid tumors. Because T-cells are not able to penetrate tumors’ fibrous barriers, Dr. Mitchell and his colleagues have turned to another part of the immune system for help.

“A macrophage is another type of immune cell of the innate immune system, the system that responds first to infections or wounds in our bodies,” Dr. Mitchell said. “These cells are characterized by their response to invaders: they engulf foreign substances and create a barrier between them and the rest of the body.”

Macrophages, literally “big eaters,” will naturally swarm to a splinter or bacterial infection; the inflammation that forms around them is the result of them trying to swallow or surround the invaders. However, macrophages will also attack benign or helpful foreign objects, like transplanted organs, medical implants, IVs, or cosmetic piercings.

While this immune response can hinder medical care, Dr. Mitchell and his colleagues are counting on it. Their research aims to give macrophages a new purpose: engulfing nanoparticles to engineer macrophages to target and kill tumor cells.

In an effort to share this research in a more engaging and tangible way, Dr. Mitchell and his graduate students are planning to bring live nanoparticle demonstrations to the Franklin Institute, offer research internships for high school students and present at the International Summer School in Greece.

“It is very important to invest in public outreach on our work in immunotherapy and vaccine development because it helps to build trust in our community and removes some of the fear of the unknown,” said Dr. Mitchell. “And we want to share our work in engaging ways while opening avenues into STEM studies for younger generations. We are excited to do that through workshops on how to make nanoparticles and interactive LEGO demonstrations that help people understand nanoparticle-cell interactions.”