Researchers at USC have figured out how to grow an unlimited supply of immune cell precursors in the laboratory, a breakthrough that could transform how doctors treat cancer and other diseases.
The discovery centers on granulocyte-monocyte progenitors, or GMPs, cells that normally sit early in the development pipeline that produces macrophages and other infection-fighting immune cells. For years, scientists dismissed GMPs as temporary stepping stones in cell development. The USC team showed they are far more valuable than anyone realized.
Published in Cell, the study demonstrates that GMPs can renew themselves indefinitely under the right laboratory conditions, a trait previously thought to belong only to stem cells. That self-renewal capacity is the key that unlocks their potential as a renewable factory for producing engineered immune weapons.
"The prevailing view has been that long-term self-renewal in the blood system is primarily a property of hematopoietic stem cells," said Qi-Long Ying, the study's corresponding author and a professor at USC's Keck School of Medicine. "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."
Why GMPs matter more than mature macrophages comes down to practicality. Macrophages naturally hunt down and consume cancer cells, making them attractive candidates for cancer therapy. But growing mature macrophages in large quantities is difficult. They resist genetic engineering, fall apart when frozen, and tend to accumulate in the lungs and liver rather than spreading throughout the body where they are needed.
GMPs sidestep these problems. Because they sit earlier in the developmental chain, they are easier to manipulate genetically and more resilient to laboratory processing. The USC team used a chemical cocktail to prevent GMPs from prematurely maturing into other cell types, allowing them to expand for extended periods while maintaining their core function.
The researchers then took the next step: they equipped GMPs with a CAR receptor, a genetic modification that acts like a molecular sight, allowing the cells to recognize and target cancer cells. They also added a second genetic signal designed to activate neighboring immune cells and supercharge the body's natural tumor-fighting defenses.
When tested in mice with blood cancers and solid tumors, the engineered GMPs slowed disease progression. Cells carrying both the targeting receptor and the immune-boosting signal performed even better. Critically, the GMPs settled into the bone marrow and continued generating engineered macrophages, solving a major weakness that has plagued earlier therapies based on mature macrophages, which typically fade quickly.
The advantage extends to the clinic. Because the immune-activating signal works even when donor and recipient cells don't match genetically, hospitals could eventually use off-the-shelf treatments made from donor cells instead of creating custom therapies for each patient.
Scientists at Stanford University independently confirmed the findings, lending weight to the platform's reliability. Ravi Majeti, director of Stanford's Institute for Stem Cell Biology and Regenerative Medicine, noted that the method opens doors to applications that mirror the success of engineered T cell therapies.
The technology may reach beyond cancer. When researchers tested it in mice with a chronic immune deficiency disorder, GMP treatment restored the animals' ability to fight bacterial infections, suggesting the platform could address genetic immune diseases as well.
Author Jessica Williams: "This is the kind of foundational advance that quietly reshapes an entire field, turning a cellular afterthought into a manufacturing engine for precision medicine."
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