USC Scientists Develop Method for Unlimited Supply of Cancer-Fighting Immune Cells

A New Approach to Cancer Immunotherapy

Researchers at the University of Southern California (USC) Stem Cell have developed a technique to produce an unlimited supply of immune cell precursors, potentially revolutionizing cancer immunotherapy. The study, published in the journal Cell, focuses on granulocyte-monocyte progenitors (GMPs), a type of progenitor cell that gives rise to macrophages and other immune cells.

GMP Self-Renewal Capability

A key finding is that GMPs can self-renew – a property typically associated with stem cells. Scientists previously believed that long-term self-renewal in the blood system was exclusive to hematopoietic stem cells. However, under the right conditions, GMPs can also self-renew while maintaining their ability to produce functional immune cells.

Importance of Macrophage Precursors

Macrophages are attractive candidates for cancer immunotherapy because they naturally infiltrate tumors, consume cancer cells, and help organize immune responses. However, mature macrophages have drawbacks: they are difficult to grow in large numbers, genetically engineer, and store. To overcome these obstacles, the team focused on GMPs, which are at an earlier developmental stage.

Genetic Engineering to Fight Cancer

The researchers successfully expanded GMPs in the lab and genetically modified them to recognize cancer cells. They equipped GMPs with a chimeric antigen receptor (CAR) and added a second signal to activate nearby immune cells. This allows for the creation of "off-the-shelf" therapies that can be used for many patients.

Testing in Mice

After expanding and engineering both mouse and human GMPs, the team tested them in mice. The cells successfully engrafted into bone marrow and other blood-forming tissues, continuously producing engineered macrophages and other immune cells. Mice with blood cancers and solid tumors showed slowed disease progression.

Potential Beyond Oncology

The platform may also have applications for immune deficiencies. The researchers tested it in mice with chronic granulomatous disease, and GMP treatment restored their ability to fight bacterial infections.

The study was supported by several organizations, and some authors are co-inventors on related patents and co-founders of Myelogene Inc.