Innovation Creates Renewable Source of Cancer-Fighting Immune Cells

Scientists at the University of Southern California (USC) in the United States have announced their success in developing an innovative method to produce renewable supplies of cancer-fighting immune cells, according to sciencedaily.com, citing the Keck School of Medicine of USC. The innovation, detailed in a study published in the journal Cell, relies on working with immature immune cells capable of transforming into powerful defenders, rather than relying on mature cells.

The research team focused on a type of immature cell known as granulocyte-monocyte progenitors (GMPs). Under normal conditions, these cells develop into macrophages and other immune cells that protect the body from infection and participate in immune responses. Chi-Long Young, a professor of stem cell biology and regenerative medicine at the Keck School of Medicine and corresponding author of the study, stated that “the study establishes a scalable and engineerable platform for these cells in cellular immunotherapy, and introduces concepts we believe will have broad implications for cancer immunotherapy and stem cell biology.”

The significance of this discovery extends beyond therapy; it challenges established understanding of how blood and immune cells are formed. Traditionally, long-term self-renewal capacity has been associated with hematopoietic stem cells, whereas progenitor cells are further along the developmental pathway and possess less of this ability. The researchers demonstrated that granulocyte-monocyte progenitors are capable of self-renewal under controlled laboratory conditions, continuing to proliferate while maintaining their identity and ability to produce functional immune cells.

Researchers view macrophages as a promising therapeutic tool, particularly against solid tumors, because they naturally migrate to tissues and infiltrate tumors. However, translating this into a practical treatment faces obstacles, including:

• Their tendency to accumulate in organs such as the lungs and liver rather than dispersing widely throughout the body.

To overcome this, lead author Yi Shi and colleagues in Young’s laboratory developed a precisely formulated chemical mixture that allowed progenitor cells to survive and proliferate for extended periods in the lab, preventing premature maturation. Even after large-scale expansion, the cells retained their molecular characteristics and their ability to differentiate into functional macrophages. Independently, researchers in Ravi Majeti’s laboratory at Stanford University confirmed the possibility of maintaining these cells for extended periods and genetically engineering them.

Majeti, director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine, added: “This method of expansion and engineering opens the door to numerous translational applications, such as the expansion and engineering of T cells. We have already demonstrated engineering these cells to perform multiple powerful functions, and there is much more to explore.”

The team engineered the cells to carry chimeric antigen receptors (CARs), which are engineered receptors that enable cells to recognize specific molecular markers on the surface of cancer cells. Some cells were equipped with an additional immune-activating signal that recruits and stimulates nearby immune cells, including T cells. This signal remained effective even when the immune characteristics of the donor cells did not match those of the recipient, paving the way for off-the-shelf therapies manufactured in advance from donor cells, as opposed to personalized treatments that require preparing each dose from the patient’s own cells.

• The stability of progenitor cells in the bone marrow and other sites responsible for blood cell production, allowing them to generate new macrophages and immune cells.

The researchers emphasized that cancer treatment results remain in the preclinical stage, and that further research is needed to determine the safety and efficacy of these cells in humans, particularly if the intention is for them to persist in the body and produce immune cells over a long period. Ying concluded that “the future of immunotherapy may depend not only on designing better CAR receptors, but also on selecting the appropriate developmental stage of the cell.”