Researchers Develop Renewable Immune Cell Precursors for Next-Generation Cancer Therapy

A new advance in immunology could transform how doctors develop cell-based therapies for cancer and other serious diseases. Scientists have identified a way to reliably expand and genetically engineer progenitor cells that give rise to macrophages, key immune cells capable of attacking cancer.

Macrophages are specialized white blood cells that patrol tissues, engulf cancer cells, pathogens, and cellular debris. They also help coordinate immune responses by releasing signaling molecules that activate other immune cells, making them an attractive target for next-generation immunotherapies.

Macrophages and Their Untapped Potential

Despite their important role within tumors, macrophages have proven difficult to use as therapeutic tools. Unlike other immune cells, they do not grow well outside the body, are challenging to freeze and store, and often lose their function after prolonged laboratory culture.

By comparison, T cells can be expanded and genetically modified much more reliably, which has enabled the success of CAR-T cell therapies against several blood cancers. However, CAR-T treatments have shown limited effectiveness against many solid tumors, where macrophages naturally outnumber T cells and play a central role in the tumor environment.

The new study, led by researchers at the University of Southern California in collaboration with Stanford University, focused on an earlier stage of immune cell development. Instead of engineering mature macrophages, the scientists targeted granulocyte-monocyte progenitors (GMPs), the precursor cells that give rise to macrophages and several other immune cell types.

Creating a Renewable Source of Immune Cells

GMPs are not stem cells, but they represent an important intermediate stage in blood cell development. The researchers demonstrated that, under carefully optimized laboratory conditions, these progenitor cells could repeatedly divide while maintaining their identity.

Using a precisely controlled combination of growth factors and signaling molecules, the team successfully induced both mouse and human GMPs to undergo extensive self-renewal. Importantly, the expanded cells retained their ability to mature into fully functional macrophages and related immune cells.

This breakthrough provides a scalable platform for future cell therapies. Rather than relying on fragile mature macrophages with limited lifespan, researchers may now be able to engineer a renewable population of progenitor cells that can continuously generate therapeutic immune cells.

Toward Next-Generation CAR-M Therapies

The scientists next introduced chimeric antigen receptors (CARs) into the expanded GMPs, creating a macrophage-based platform often referred to as CAR-M therapy. In laboratory experiments, these genetically modified progenitor cells consistently produced macrophages capable of recognizing and attacking cancer cells.

When transplanted into mice with both blood cancers and solid tumors, the engineered GMPs distributed throughout the body and continued generating macrophages and other immune cells over time. This sustained production was associated with slower tumor growth in both circulating and solid cancers.

Unlike infusions of mature macrophages, which typically survive only briefly and remain near the injection site, progenitor-derived therapies may provide broader distribution and longer-lasting immune activity throughout the body.

Broader Implications for Immunotherapy

Researchers believe the findings could establish a new branch of cell-based immunotherapy alongside CAR-T treatment. Just as reliable T-cell engineering revolutionized therapy for certain blood cancers, the ability to expand and modify GMPs could support the development of macrophage-centered treatments for a wider range of diseases.

Beyond cancer, engineered GMPs could potentially be designed to fight chronic infections, regulate excessive inflammation, or promote tissue repair. Each of these applications would require carefully tailored genetic modifications and extensive safety testing.

The study also highlights the importance of selecting the appropriate developmental stage for immune-cell engineering. Working with progenitor cells rather than fully mature immune cells may provide greater flexibility, improved durability, and enhanced therapeutic potential.

Next Steps Before Clinical Use

Although the results in animal models are encouraging, the researchers emphasize that significant work remains before the approach can be tested routinely in patients. Human clinical trials will be needed to evaluate safety, effectiveness, manufacturing feasibility, and potential risks, including uncontrolled cell growth and unintended immune responses.

Published in the journal Cell, the study represents an important step toward more versatile and durable immunotherapies. If future clinical trials confirm these findings, engineering renewable progenitor cells could provide an effectively unlimited source of cancer-fighting immune cells for treating both blood cancers and solid tumors.