Accelerating CAR T cell therapy: Lipid nanoparticles speed up manufacturing

Penn Engineers have developed a novel method for manufacturing CAR T cells using lipid nanoparticles as delivery vehicles.

For patients with certain types of cancer, CAR T cell therapy has been nothing short of life changing. Developed in part by Carl June, Richard W. Vague Professor at the Perelman School of Medicine, and approved by the Food and Drug Administration (FDA) in 2017, CAR T cell therapy mobilizes patients’ own immune systems to fight lymphoma and leukemia, among other cancers.

Microscopic view of lipid nanoparticles.
Image: iStock/Love Employee

However, the process for manufacturing CAR T cells themselves is time-consuming and costly, requiring multiple steps across days. The process involves extracting patients’ T cells, then activating them with tiny magnetic beads, before giving the T cells genetic instructions to make chimeric antigen receptors (CARs), the specialized receptors that help T cells eliminate cancer cells.

Now, Penn Engineers have developed a novel method for manufacturing CAR T cells, one that takes just 24 hours and requires only one step, thanks to the use of lipid nanoparticles (LNPs), the potent delivery vehicles that played a critical role in the Moderna and Pfizer-BioNTech COVID-19 vaccines.

In a new paper in Advanced Materials, Michael J. Mitchell, associate professor in bioengineering, describes the creation of “activating lipid nanoparticles” (aLNPs), which can activate T cells and deliver the genetic instructions for CARs in a single step, greatly simplifying the CAR T cell manufacturing process. “We wanted to combine these two extremely promising areas of research,” says Ann Metzloff, a doctoral student and graduate research fellow in the Mitchell lab and the paper’s lead author. “How could we apply lipid nanoparticles to CAR T cell therapy?”

Metzloff also sees additional potential for aLNPs. “I think aLNPs could be explored more broadly as a platform to deliver other cargoes to T cells,” she says. “We demonstrated in this paper one specific clinical application, but lipid nanoparticles can be used to encapsulate lots of different things: proteins, different types of mRNA. The aLNPs have broad potential utility for T cell cancer therapy as a whole, beyond this one mRNA CAR T cell application that we’ve shown here.”

This story is by Ian Scheffler. Read more at Penn Engineering Today.