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One of the most powerful cancer treatments ever invented has a supply problem: it has to be built, one batch at a time, from each patient's own cells. A team led by USC Stem Cell scientists thinks it has found a way around that - by growing a renewable, freezable supply of immune cells that can be engineered to hunt tumors and rally the body's own defenses. The work, published in Cell, is still early and tested only in mice. But the idea at its center - that you can take a committed immune-cell progenitor and make it multiply almost indefinitely - could reshape how cell therapies are made.
- Who: USC Stem Cell / Keck School of Medicine of USC, with Stanford, Creighton University, and Harvard Medical School / Dana-Farber. First author Shi Yue; senior author Qi-Long Ying; Stanford co-author Ravi Majeti.
- What: a method to expand granulocyte-monocyte progenitors (GMPs) - blood cells that make macrophages - so they self-renew long-term, a trait thought to belong only to stem cells.
- The upgrade: the GMPs were engineered with a CAR (to recognize cancer) plus an extra immune-activating signal (to recruit the body's own T cells).
- Result (mice): slowed both blood cancers and solid tumors; both upgrades together beat either alone; and in a separate inherited immune disease, restored the ability to fight infection.
- Why it matters: renewable + freezable + tolerant of donor-recipient mismatch points to off-the-shelf cell therapy - made once, given to many.
- Status: preclinical; Cell, published June 19, 2026; DOI 10.1016/j.cell.2026.05.043.
1. The problem: a miracle therapy that does not scale
CAR-T cell therapy has produced some of the most dramatic results in modern oncology, driving certain advanced blood cancers into deep remission. But every dose is essentially a bespoke product: a patient's own T cells are drawn, genetically reprogrammed in a specialized facility to carry a chimeric antigen receptor (CAR) that recognizes their cancer, grown up, and infused back. That custom build makes the therapy slow to produce and expensive, and it limits how many people can be treated. T cells also tend to perform best against blood cancers and struggle to break into the dense environment of solid tumors.
For years, researchers have chased an alternative: an off-the-shelf immune cell that could be manufactured in advance, frozen, and given to many patients on demand. The hard part is having a cell source that does not run out.
2. The trick: teaching a progenitor to renew itself
The USC-led team changed which cell they started from. Instead of a finished T cell, they reached one step back in development, to granulocyte-monocyte progenitors (GMPs) - committed blood cells that naturally give rise to macrophages, monocytes, and neutrophils, the front-line cells of the innate immune system.
Using a defined culture system - a tailored chemical environment - they coaxed GMPs to keep dividing extensively in the lab while holding onto their identity, instead of maturing and burning out. In other words, the progenitors gained long-term self-renewal, the hallmark capability normally reserved for blood (hematopoietic) stem cells.
In the textbook picture, only hematopoietic stem cells can self-renew indefinitely; their progeny, like GMPs, are supposed to divide a limited number of times and then differentiate. Senior author Qi-Long Ying summed up the surprise: “The prevailing view has been that long-term self-renewal in the blood system is primarily a property of the 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.” A self-renewing progenitor is, in effect, a renewable factory: you can expand it, bank it, freeze it, and engineer it.
3. Two upgrades: aim, and amplify
With a renewable cell in hand, the team added two pieces of engineering:
- A CAR - a synthetic receptor that lets the cell recognize a specific marker on cancer cells, the same core idea behind CAR-T.
- An extra immune-activating signal - a second modification designed to engage nearby immune cells and switch on the body's own tumor-fighting T cells, so the engineered cells do not act alone.
The result is a macrophage-lineage cell that can both attack a tumor directly and help recruit a broader immune response around it.
4. What happened in the mice
| Model | What the engineered GMPs did |
|---|---|
| Blood cancer | CAR-engineered GMPs slowed disease progression; cells with both upgrades did better still. |
| Solid tumors | Same pattern - a meaningful effect in the setting where T-cell therapies usually struggle. |
| Chronic granulomatous disease | In this inherited immune disorder, the GMPs restored the animals' ability to fight bacterial infection. |
That last result is a hint that the platform reaches beyond cancer: because GMPs make macrophages and neutrophils, a renewable, engineerable supply could matter for immune deficiencies and other diseases too.
5. Why progenitors, not finished macrophages
Mature macrophages are notoriously hard to use as a drug: they are difficult to expand in large numbers, hard to genetically engineer, fragile to freeze and store, and they tend to be cleared from the body quickly. Starting from a renewable progenitor flips each of those problems. The GMPs engraft in the bone marrow and keep producing fresh engineered macrophages over time, rather than being a one-and-done infusion.
Crucially, the team reported that the immune-activating design still works even when donor and recipient are immunologically mismatched. That is the key to an off-the-shelf product: cells made from a donor could, in principle, be banked and given to many patients, instead of manufacturing a unique batch for each person. As Stanford's Ravi Majeti put it, “This method for the expansion and engineering of GMPs opens the door to numerous translational applications, much like T cell expansion and engineering.”
- Preclinical. Every result here is in mice. No human trials have begun.
- Slowed, not cured. The paper reports delayed disease progression and added benefit from the dual design - encouraging signals, not cures.
- Durability and safety in people are unproven. Engrafting, self-renewing cells must be shown to be controllable and safe over the long term in humans.
- Commercial interests. Several authors hold patents licensed to, and co-founded, a startup built around the technology - context worth knowing, even though it does not change the biology.
What this could mean
The deeper idea in the paper is a shift in mindset. As Ying framed it, “the future of immunotherapy may depend not only on designing better CAR receptors, but also on choosing the right developmental stage of the cell.” Much of the field has focused on building smarter receptors; this work suggests that which cell you start from - and whether it can renew itself - may matter just as much.
If the approach holds up in larger animals and then in people, the payoff is not a single new drug but a manufacturing change: cancer cell therapies that are cheaper, faster to produce, and available to far more patients than today's bespoke approach allows. That is still a long road. But it is a hopeful one.
Sources
- USC Stem Cell (primary press release): A renewable cell source for cancer immunotherapy and beyond
- Shi Yue, Qi-Long Ying, Ravi Majeti, et al., “Expansion and CAR engineering of granulocyte-monocyte progenitors for cellular immunotherapy,” Cell, June 19, 2026 - DOI 10.1016/j.cell.2026.05.043
- EurekAlert release · MedicalXpress coverage · ScienceDaily
Curated by Jerry Cards - jerrycards.com. We research the week's most consequential science, health, and tech news so you don't have to. More at jerrycards.com/news.