USC scientists just unlocked an endless supply of cancer-fighting immune cells

Cell-based immunotherapies have transformed the treatment of certain blood cancers, but extending these successes to solid tumors remains a major challenge. A new study from USC Stem Cell, published in Cell, suggests that looking earlier in the immune cell developmental pathway may provide a new solution.

Rather than engineering mature immune cells, the research team focused on granulocyte-monocyte progenitors (GMPs)—precursor cells capable of generating macrophages and other immune cells. Led by Dr. Qi-Long Ying at the Keck School of Medicine of USC, the researchers developed a method to expand GMPs extensively in the laboratory while preserving their ability to continuously produce functional immune cells.
The work challenges a long-standing assumption in stem cell biology. Self-renewal has traditionally been viewed as a defining feature of hematopoietic stem cells, whereas progenitor cells were thought to have only limited capacity for long-term expansion. Under carefully defined culture conditions, however, the researchers demonstrated that GMPs can repeatedly divide while maintaining both their identity and their immune-producing potential.

Beyond scalable expansion, the team also engineered GMPs with chimeric antigen receptors (CARs) to recognize cancer cells. An additional immune-activating signal further strengthened anti-tumor responses by recruiting surrounding immune cells, including those involved in activating tumor-fighting T-cells.

In mouse models of both blood cancers and solid tumors, the engineered GMPs established themselves within bone marrow, continuously generating cancer-fighting immune cells over time. This sustained production addresses one of the key limitations of mature macrophage therapies, which often decline rapidly after administration. Notably, the additional immune-activating signal remained effective even when donor and recipient cells were immunologically mismatched, supporting the possibility of future off-the-shelf cellular therapies.

The platform also demonstrated broader therapeutic potential. In a mouse model of chronic granulomatous disease, GMP treatment restored the animals’ ability to combat bacterial infections, suggesting applications beyond oncology.

As Dr. Ying notes, “the future of immunotherapy may depend not only on designing better CAR receptors, but also on choosing the right developmental stage of the cell.”

While these findings remain preclinical, they highlight an important shift in thinking. Future advances in cellular immunotherapy may come not only from improving engineered receptors, but also from selecting more versatile cellular starting materials that combine scalability, durability, and broader therapeutic potential.

Research article: