Shi Yue stared at the petri dish where tiny clusters of cells pulsed with potential—each one a granulocyte-monocyte progenitor (GMP) that could one day become a macrophage engineered to hunt down solid tumors like breast cancer. At the Ying Lab in Los Angeles, this moment marked the culmination of years of work: a renewable, scalable source of immune progenitor cells that might finally unlock off-the-shelf immunotherapies for cancers that have long resisted treatment.
Most immunotherapies today rely on T cells, which have transformed outcomes for blood cancers but struggle to penetrate dense solid tumors. Macrophages, by contrast, naturally infiltrate these tumors, engulf cancer cells, and rally other immune soldiers—but manufacturing them at scale has been nearly impossible. They don’t multiply well outside the body, resist genetic tweaks, and often get trapped in the liver or lungs instead of reaching their targets. That’s why the USC Stem Cell team, led by Dr. Qi-Long Ying, turned upstream—to GMPs, the precursors that give rise to macrophages.
In a breakthrough published in Cell, the team revealed they could expand GMPs indefinitely in the lab using a precise chemical cocktail that blocked premature maturation. Even after months of growth, these progenitor cells retained their identity and ability to generate functional immune cells. Crucially, they also demonstrated that GMPs—once thought incapable of long-term self-renewal—could divide extensively without losing their potency, a feat previously believed exclusive to hematopoietic stem cells. “We found that, under the right conditions, GMPs can also self-renew, dividing extensively while keeping their identity and ability to produce functional immune cells,” said Ying. “That gives us a scalable starting point for engineering cell therapies for cancer, infectious disease, and potentially many other conditions.”
The team went further: they genetically engineered the GMPs to express chimeric antigen receptors (CARs), guiding them to recognize specific cancer markers. When these CAR-GMPs matured into macrophages, they effectively targeted and destroyed breast cancer cells in lab models. The platform was independently validated by Dr. Ravi Majeti’s lab at Stanford, reinforcing its reliability for future clinical use.
This innovation could democratize access to cell therapies. Unlike personalized T-cell treatments, which take weeks to manufacture for each patient, GMP-based therapies could be produced in bulk, frozen, and distributed like medicine on a shelf. With solid tumors—such as those in breast, lung, and pancreatic cancers—accounting for over 90% of cancer deaths, the need for scalable solutions has never been greater. Now, for the first time, scientists have a renewable cellular engine that can be programmed, preserved, and deployed. As research moves toward clinical trials, the vision is clear: a future where potent, engineered immune cells are no longer a luxury for the few, but a readily available weapon against cancer for all.