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Gel Boosts T-Cells for Cancer Treatments

T-cells illustration

T-cells (NASA.gov)

19 Apr. 2019. A biomedical engineering team devised techniques using a gel to produce more engineered T-cells, which in lab mice stopped the growth of tumors. Researchers from Johns Hopkins University in Baltimore describe their techniques in the 10 April issue of the journal Advanced Materials (paid subscription required).

The study, led by doctoral candidate John Hickey, seeks more efficient and productive methods for culturing and generating T-cells as treatments for disease. T-cells, white blood cells in the immune system, are being captured from patients and engineered to add cancer-fighting proteins in treatments for blood-related and solid-tumor cancers, including some therapies cleared by FDA. Among these added proteins are chimeric antigen receptors, proteins attracting antibodies that bind to and destroy cancer cells.

While theses therapies are effective in some cases, they’re complicated, expensive, and time-consuming to carry out. T-cells must first be extracted from the patient, then cultured for 6 to 8 weeks in the lab, before being returned to the patient. And after that, engineered T-cells work for only limited periods of time.

Hickey, and colleagues from the labs of Johns Hopkins pathology professor Jonathan Schneck and biomaterials engineering professor Hai-Quan Mao, take a different approach, by creating a different culturing environment that stimulates more T-cells in the lab, and at higher speed. Their solution uses a hydrogel, a water-based biocompatible polymer, containing hyaluronic acid, a natural ingredient found in skin and other soft tissue. Into the mix, they add materials to emulate the extracellular matrix, the framework for cells, as well as proteins that promote cell signaling, making the T-cells better cancer fighters.

That culturing media, say the researchers, is crucial for T-cell production. “We believe that a T-cell’s environment is very important,” says Hickey in a university statement. “Biology doesn’t occur on plastic dishes. It happens in tissues.” The Johns Hopkins team tested T-cell activity in the hydrogel against plain plastic dishes, and found cells cultured in hydrogel produced 50 percent more signaling enzymes called cytokines than cells grown in plastic dishes.

The researchers also tested different properties of hydrogels, and found the softer the gel, the more T-cells it produced. In the softest hydrogels, a few seeded T-cells multiplied into 150,000 cells, a quantity sufficient for cancer therapies, in 7 days. In that same period, conventional cell culturing methods produce only about 20,000 cells.

The team then tested T-cells produced in the hydrogel as cancer treatments. Cells produced in hydrogel were injected into lab mice induced with melanoma, an aggressive form of skin cancer. The results show tumor size stabilized in mice receiving the hyrogel-produced T-cells, with the mice surviving more than 40 days. Mice receiving T-cells cultured in plastic dishes, however, show continued tumor growth and survival times of about 30 days.

The researchers believe the T-cell promoting gel can be the basis of an eventual medical device that acts like lymph nodes in the body to activate and promote production of immune system cells. “As we perfect the hydrogel and replicate the essential feature of the natural environment, including chemical growth factors that attract cancer-fighting T-cells and other signals,” notes Schneck, ” we will ultimately be able to design artificial lymph nodes for regenerative immunology-based therapy.”

The university says the authors filed for a patent on the hydrogel technology.

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