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Nanoparticles Boost T-Cells to Fight Leukemia

Matthias Stephan

Matthias Stephan (Stephan Lab)

18 April 2017. A cancer research lab designed a process to treat leukemia by reprogramming cells in the immune system with genes on nanoscale biodegradable particles. The team from Fred Hutchinson Cancer Research Center in Seattle describes its discovery and tests with lab mice in yesterday’s issue of the journal Nature Nanotechnology (paid subscription required).

Researchers from the lab of Matthais Stephan, and colleagues from University of Washington, are seeking more practical and reliable ways of engineering T-cells from the immune system with chimeric antigen receptors, proteins attracting antibodies that bind to and destroy blood-related cancer cells. Current methods producing chimeric antigen receptor T-cells, known as CAR T-cells, produce promising results in clinical trials in patient with leukemia and other blood-related cancers.

But the current process is also time-consuming and dangerous for some patients. T-cells are taken from patients, then genetically engineered and cultured in the lab, for later infusion back into the individual, which can take several weeks to produce sufficient numbers of cells. Before the re-engineered cells can be introduced, patients must also undergo chemotherapy both as a cancer therapy, and to remove other immune system cells that can dilute the potency of the infused re-engineered T-cells. As reported in Science & Enterprise, chemotherapy treatments that precede CAR T-cell infusions were responsible for deaths of patients in clinical trials from cerebral edemas, or swelling in the brain.

Stephan and colleagues designed a more straightforward process that reprograms T-cells with genes encoding chimeric antigen receptors, and carried into the patient with nanoparticles made from a biodegradable polymer. The nanoparticles also contain molecules that attract and then bind to the T-cells, causing the receiving cells to engulf and take in the genes with chimeric antigen receptors. The CAR-encoding genes then integrate with the cells’ chromosomes and become CAR T-cells for battling blood-related cancers. The researchers say with this process, T-cells can transform into CAR T-cells in 24 to 48 hours.

The Fred Hutch team tested its process in lab mice induced with leukemia. Infusions with the CAR nanoparticles caused leukemia in the mice to go into remission, and extended survival of the mice to a median of more than 8 weeks, where the mice would normally survive only about 2 weeks. Chemotherapy was not used with the CAR nanoparticles.

The authors say production of the CAR-laden nanoparticles is relatively simple using stable polymer materials, which makes them easier to transport and store, in addition to being a faster process than before. The researchers believe the process can be engineered into a platform technology to more efficiently produce other cancer immunotherapies, as well as treatments for infectious diseases that harness cells in the immune system.

Fred Hutchinson Center says Stephan is working with companies with facilities to produce clinical-grade nanoparticles like those used in the study. Fred Hutch also filed for U.S. and international patents on the process, with Stephan listed as inventor.

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