USC develops method to grow immune cells against cancer — ScienceDaily
Researchers at the University of Southern California (USC) have developed a method for long-term cultivation and genetic modification of immune cell precursors. In experiments in mice, these cells settled in the bone marrow, generated new immune cells, and slowed the progression of blood cancers and solid tumors, ScienceDaily reports.
Precursors instead of mature macrophages
The USC Stem Cell team worked with granulocyte-monocyte progenitors, or GMPs. Under normal conditions, they can develop into macrophages and other immune system cells. The scientists selected a specific mixture of chemicals that allowed GMPs to survive and multiply in the laboratory for a long time without maturing prematurely.
According to the researchers, even after substantial expansion under laboratory conditions, GMPs retained their molecular characteristics and their ability to form functional macrophages and related cells. This could remove some of the manufacturing limitations of therapies based on mature macrophages: such cells are difficult to culture at scale, genetically modify, freeze, and store.
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CAR receptors and mouse trials
The scientists equipped GMPs with a chimeric antigen receptor, or CAR, which enables immune cells to recognize a specific marker on the surface of cancer cells. Some of the cells were also supplemented with a signal to recruit and activate other immune cells, including T cells. This signal remained effective even when the donor's and recipient's immune characteristics did not match, potentially opening the way for pre-manufactured cell products.
After being administered to mice, the modified precursors engrafted in the bone marrow and other blood-forming sites, where they could generate new engineered macrophages and related cells. GMPs with CAR receptors slowed the course of cancer in models of blood cancer and solid tumors. Combining CAR with an additional immune-activating signal enhanced the antitumor response.
The results are still preclinical
The authors also tested the approach in a mouse model of chronic granulomatous disease, an inherited disorder in which certain immune cells cannot effectively destroy microorganisms. Administering GMPs restored the animals' ability to fight a bacterial infection. The study was published in the journal Cell; its cancer-treatment findings are currently preclinical and require further safety and efficacy testing in humans.
