Endless Supply of Engineered Macrophage Progenitors Offers New Hope for Cancer Immunotherapy

Scientists at the University of Southern California (USC) have genetically modified granulocyte-monocyte progenitors (GMPs)—the cells that give rise to macrophages—to self-renew in culture. By supplying a defined cocktail of chemicals at precise stages, the team produced an expandable source of progenitors that can be engineered to express chimeric antigen receptors (CAR-M). When injected into mice bearing blood-cancer or solid-tumor grafts, the GMPs migrated throughout the body, differentiated into functional macrophages, and slowed tumor progression more effectively than directly injected macrophages.

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CAR-T therapy, which reprograms a patient’s T cells, has shown strong results in hematologic cancers but performs poorly against solid tumors. Macrophages are the most abundant immune cells within solid tumors, yet they have been difficult to culture, engineer, and store. The USC approach targets the progenitor stage rather than mature macrophages, aiming to overcome these limitations and broaden the applicability of CAR-based immunotherapies.

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The work was led by biologist Qi-Long Ying at USC, with collaboration from Ravi Majeti of Stanford University. Their findings were published in *Cell* (Yue et al., 2026). The study involved both mouse and human GMPs to demonstrate cross-species feasibility.

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Under the right culture conditions, the modified GMPs displayed extensive self-division while retaining their identity and capacity to generate functional immune cells. Engineered GMPs were programmed to produce CAR-M cells, which, unlike injected mature macrophages, proliferated systemically after transplantation. In murine models, this resulted in a sustained supply of macrophages and auxiliary immune cells that collectively impeded tumor growth in both hematologic and solid-tumor settings.

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The ability to mass-produce self-renewing GMPs could provide a scalable platform for CAR-M therapies, potentially enabling treatment of solid tumors that have resisted existing immunotherapies. The approach also suggests that targeting earlier developmental stages of immune cells may improve the durability and reach of engineered cell therapies across a range of diseases.

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Ying emphasized that demonstrating self-renewal in progenitor cells challenges the prevailing view that long-term blood-system renewal is limited to stem cells, and that this property offers a “scalable starting point” for engineering cell therapies. Majeti highlighted that the GMP expansion method opens “numerous translational applications,” comparable to established T-cell expansion techniques, and noted that the team has already shown multiple potent engineered functions while acknowledging further exploration is needed.

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• “The prevailing view has been that long-term self-renewal in the blood system is primarily a property of the …” — Qi-Long Ying, Biologist, USC

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• “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.” — Qi-Long Ying, Biologist, USC

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• “ "That gives us a scalable starting point for engineering cell therapies for cancer, infectious disease, and potentially many other conditions.” — Qi-Long Ying, Biologist, USC

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• “This method for the expansion and engineering of GMPs opens the door to numerous translational applications, much like T cell expansion and engineering,” — Ravi Majeti, Biologist, Stanford University

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• “We have already demonstrated engineering of these cells to drive multiple potent functions, and there is a lot more to be explored.” — Ravi Majeti, Biologist, Stanford University

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• “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,” — Qi-Long Ying, Biologist, USC

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The researchers plan to refine the chemical cocktail for GMP expansion, test additional CAR designs, and evaluate safety and efficacy in larger animal models. Translating the platform to human clinical trials will require further validation of manufacturing protocols and regulatory assessment before potential therapeutic use.

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