Researchers at the University of Southern California developed a method to create a renewable supply of granulocyte-monocyte progenitors (GMPs) that can be engineered to fight cancer. Published in the journal Cell on June 19, 2026, the study demonstrates that these immune cell precursors can self-renew in a lab, providing a scalable platform for immunotherapy.
How GMPs solve the macrophage production bottleneck
Photo: ThePrint
Macrophages are the immune system’s professional phagocytes, designed to engulf cancer cells and coordinate broader immune responses. While they are highly effective at infiltrating the dense environments of solid tumors, they have historically been a nightmare to use in clinical settings. According to ScienceDaily, mature macrophages are difficult to grow in large numbers outside the body, hard to genetically engineer, and often sustain damage during freezing and storage.
Even when successfully infused, mature macrophages tend to clump in the liver and lungs rather than spreading throughout the body. This limitation has stalled the development of CAR-M (Chimeric Antigen Receptor Macrophage) therapies. To bypass these hurdles, Dr. Qi-Long Ying and his team at the Keck School of Medicine of USC shifted their focus one step back in the developmental chain to granulocyte-monocyte progenitors, or GMPs.
By using a specific chemical cocktail to block the cells’ internal differentiation programs, the researchers kept the GMPs in a precursor state. This allowed the cells to proliferate indefinitely while maintaining their ability to produce functional macrophages.
“The prevailing view has been that long-term self-renewal in the blood system is primarily a property of the … stem cells that can generate any type of blood or immune cell. We found that, under the right conditions, [progenitors] can also self-renew, dividing extensively while keeping their identity and ability to produce functional immune cells.”
Dr. Qi-Long Ying, professor of stem cell biology and regenerative medicine at the Keck School of Medicine of USC, via ScienceDaily
Comparing GMP platforms to existing CAR-T therapies
Photo: ScienceDaily
The medical community has seen massive success with CAR-T cell therapy, particularly for blood cancers. However, Tech Times reports that no CAR-T therapy has yet been approved for solid tumors, which represent approximately 90 percent of cancers globally. T cells often struggle to penetrate the immunosuppressive ecosystem surrounding solid tumors—a barrier macrophages are naturally built to cross.
The current manufacturing model for macrophage therapy is also prohibitively expensive and slow. A Phase 1 trial for CT-0508, reported in February 2025 in Nature Medicine, relied on a patient’s own monocytes. This autologous approach is the same one that drives CAR-T costs to between $300,000 and $500,000 per patient dose.
Feature
Mature Macrophage Therapy
USC GMP Platform
Scalability
Difficult to expand in lab
Indefinite self-renewal
Distribution
Clumps in lungs and liver
Spreads throughout body
Production
Patient-specific (Autologous)
Potential “Off-the-shelf” (Donor)
Target
Primarily solid tumors
Solid tumors, blood cancer, infection
Results from animal trials and independent validation
UArizona scientists working to crack the cancer code
The USC team engineered GMPs with chimeric antigen receptors (CARs) to target specific tumor antigens and added a secondary signaling system to alert other immune cells. When injected into the bone marrow of mice, these GMPs created a persistent reservoir of tumor-targeting cells.
According to ThePrint, the engineered cells successfully suppressed HER2-positive solid tumors and CD19-positive leukaemia, significantly improving survival rates in the animal models. Unlike mature macrophages, which are cleared quickly from the system, the GMPs established a long-term presence.
The reliability of this platform was further confirmed through independent reproduction. Dr. Ravi Majeti at Stanford University’s Institute for Stem Cell Biology and Regenerative Medicine validated the long-term maintenance and genetic engineering of the GMPs.
“This method for the expansion and engineering of GMPs opens the door to numerous translational applications, much like T cell expansion and engineering,”
Dr. Ravi Majeti, Director of the Institute for Stem Cell Biology and Regenerative Medicine at Stanford University, via ScienceAlert
Applications beyond oncology
While the primary focus is cancer, the ability to scale and engineer these progenitors has implications for other systemic diseases. Tech Explorist notes that the platform’s effectiveness extended to treating primary immunodeficiencies. Specifically, the researchers demonstrated that GMPs could restore the ability to clear bacterial infections in mice modeling chronic granulomatous disease.
This versatility suggests a shift in immunotherapy strategy. Instead of designing a better receptor for a mature cell, the future may depend on choosing the right developmental stage of the cell to engineer. Because GMPs can be produced in advance from donor cells, this could move the industry away from expensive, patient-specific manufacturing toward a ubiquitous, off-the-shelf administration model.
“Our study suggests that the future of immunotherapy may depend not only on designing better CAR receptors, but also on choosing the right developmental stage of the cell,”
Dr. Qi-Long Ying, senior author, via ScienceAlert
<!– /wp:quote According to the senior author Dr. Qi-Long Ying, the future of immunotherapy may depend not only on designing better CAR receptors, but also on choosing the right developmental stage of the cell.
Adrian has a background in tech reporting and product analysis, previously working in Silicon Valley. He leads the technology section, covering innovation, cybersecurity, AI, and emerging digital industries.
