Scientists at the USC Stem Cell lab have developed a groundbreaking method to create a limitless, renewable supply of immune-cell precursors that can be genetically engineered to hunt and destroy cancer, potentially transforming how we treat a wide range of malignancies.
Published in the journal Cell, the study focuses on granulocyte-monocyte progenitors (GMPs) — early-stage cells that give rise to macrophages and other immune cells. Macrophages are nature's cleanup crew: they engulf invaders, consume cancer cells, and orchestrate broader immune responses.
'The study establishes a scalable and engineerable GMP platform for cellular immunotherapy and introduces concepts that we believe could have broad implications for both cancer immunotherapy and stem cell biology,' said Dr. Qi-Long Ying, professor of stem cell biology at the Keck School of Medicine of USC.
The key breakthrough is that GMPs, which scientists previously thought could not self-renew long-term, can in fact do so under the right conditions. Using a carefully defined chemical cocktail, the team prevented GMPs from maturing prematurely and succeeded in maintaining and expanding them over long periods in the laboratory.
'We found that, under the right conditions, GMPs can self-renew, dividing extensively while keeping their identity and ability to produce functional immune cells,' said Ying. 'That gives us a scalable starting point for engineering cell therapies.'
Mature macrophages are notoriously difficult to grow in large numbers and hard to genetically engineer. GMPs overcome all these limitations. The team equipped GMPs with a chimeric antigen receptor (CAR) — the same technology behind breakthrough CAR-T cell therapies — enabling the cells to recognize specific markers on cancer cells. They also added a second signal that activates nearby immune cells.
Crucially, this second signal works even when donor and recipient cells are immunologically mismatched, raising the possibility of creating 'off-the-shelf' therapies produced in advance.
In animal studies, the engineered GMPs successfully settled into bone marrow and continuously generated cancer-killing immune cells. In mice with blood cancers and solid tumors, CAR-engineered GMPs slowed disease progression. The platform also showed promise beyond cancer: in mice with chronic granulomatous disease, GMP treatment restored the ability to fight bacterial infections.
The research was independently replicated at Stanford University. The team has filed patents licensed to Myelogene Inc., a company co-founded by the researchers.
