Researchers at the Keck School of Medicine of USC have found a way to produce a potentially renewable supply of engineered immune cells that attack cancer. The study, published in Cell, focused on immature immune cells rather than mature ones. The results are limited to animal research for now, but they address several problems that have slowed the progress of cell-based cancer treatment.
How Current Cell Therapies Work
Most engineered cell therapies in use today rely on a patient’s own T cells. Doctors collect the cells, send them to a lab where they receive a chimeric antigen receptor, or CAR, that helps them recognize a cancer marker, and then return them to the patient.
The approach has changed treatment for some blood cancers. The FDA approved the first CAR T-cell therapy in 2017, and the manufacturing process typically takes three to five weeks, according to the National Cancer Institute.
But these therapies have clear limits. They have been far less effective against solid tumors, and each dose must be made individually for a single patient.
What the USC Team Did Differently
The researchers worked with granulocyte-monocyte progenitors, or GMPs. These immature cells normally develop into macrophages, the immune cells that engulf bacteria and damaged tissue.
Macrophages are appealing for cancer treatment because they move into tissue and can enter tumors. Mature macrophages are hard to work with, though. They are difficult to grow in large numbers, resist genetic modification, can be damaged in storage, and tend to clear from the body quickly.
So the team started earlier. Using a defined chemical mixture, they kept GMPs multiplying in the lab without allowing them to mature. The cells retained their identity and could still become functioning macrophages. A Stanford laboratory independently reproduced the method, as reported by ScienceDaily.
The finding also challenges a long-held view in biology. Scientists had generally believed that long-term self-renewal in the blood system belonged mainly to hematopoietic stem cells, not to progenitor cells further along in development.
Results in Mice
The team engineered GMPs to carry CAR receptors. Some cells also received an added signal designed to recruit and activate nearby immune cells, including T cells.
The results in mice were encouraging:
- The engineered cells settled in bone marrow and continued producing new immune cells.
- CAR-equipped cells slowed the progression of both blood cancers and solid tumors.
- Cells carrying both the CAR and the added signal produced a stronger antitumor response.
- The added signal remained effective even when donor and recipient immune profiles did not match.
That last finding matters. It suggests treatments could one day be made in advance from donor cells and given to many patients, rather than manufactured one person at a time.
Potential Uses Beyond Cancer
In a separate experiment, the researchers treated mice with chronic granulomatous disease, an inherited disorder that weakens the body’s ability to kill certain microbes. The GMPs restored the animals’ ability to fight bacterial infection, which points to possible future uses against infectious diseases and inherited immune deficiencies.
What Comes Next
These results are preclinical. Researchers still need to determine whether engineered GMPs are safe in people, particularly because the cells are designed to persist and keep producing immune cells over time.
Any therapy that reaches human trials will also face a lengthy review. Recent approvals such as the first oral cholesterol pill show how much clinical evidence regulators require before a new treatment reaches patients.
This study drew support from private foundations and a biotechnology company. That arrangement is common in early-stage research, and it has drawn attention to the legal side of healthcare investments.
Cost and Access
Personalized cell therapies are expensive to produce. An off-the-shelf version could ease some of the strain these treatments place on the health care system.
Coverage decisions will shape who benefits. Insurers and government programs determine which patients can receive new therapies, and that question carries more weight amid ongoing Medicaid changes.
Progress on this research and other cancer treatment developments will continue to appear in health news as clinical work moves forward.
Patients and families following immunotherapy research can find ongoing coverage at Information Inside Road. Anyone weighing treatment options should ask their oncology care team whether a clinical trial may be appropriate.