Technologies for the directed evolution of cell therapies

In the review, Di Carlo highlights the importance of automation tools in the selection of cells with unique properties and therapeutically beneficial traits to help drive the rise of cell therapies in the clinic. "Directed evolution of proteins with unique functions and stability was recognized with the Nobel Prize in 2018, and many molecular therapeutics, such as therapeutic antibodies, rely on evolutionary processes for their development," says Di Carlo. "Cell therapies are rising as a third pillar of modern medicine along with molecular and gene therapies, with exciting opportunities given the ability of cells to sense and respond to the environment in both chemical and physical manners."

In contrast, the article also discusses the current lack of fundamental knowledge to engineer complex traits within cells. Di Carlo argues that researchers should make use of directed evolution processes of mutagenesis (epigenetic or genetic) and selection to evolve complex traits of importance for new cell therapies that can, for example, target and kill solid tumors more effectively. He identifies specific traits like cell secretion, ability to apply force, deformability, and adhesiveness as unique traits that would be important to enable infiltration and killing of solid tumors.

Emerging tools such as image-activated cell sorters and cell secretion-based sorting using droplet microfluidics are featured as ways to potentially enable high-throughput automation technologies. Di Carlo indicates that with high-throughput selection tools and directed evolution processes applied to cells, researchers could accelerate the development of cellular products with extreme therapeutic benefit.