{"id":44317,"date":"2023-01-10T13:15:23","date_gmt":"2023-01-10T18:15:23","guid":{"rendered":"https:\/\/sciencebusiness.technewslit.com\/?p=44317"},"modified":"2023-01-10T13:15:23","modified_gmt":"2023-01-10T18:15:23","slug":"nanotech-enzyme-process-boosts-t-cell-cancer-therapies","status":"publish","type":"post","link":"https:\/\/technewslit.com\/sciencebusiness\/?p=44317","title":{"rendered":"Nanotech Enzyme Process Boosts T-Cell Cancer Therapies"},"content":{"rendered":"
\"T-cells<\/a>
Killer T-cells surround a cancer cell (NICHD, Flickr)<\/figcaption><\/figure>\n

10 Jan. 2023. A bioengineering team devised techniques for feasibly adding cancer-killing enzymes to engineered immune cells that in lab mice kill solid-tumor and blood cancer cells. Researchers from the cell and tissue engineering lab of David Mooney<\/a> at Harvard University and colleagues from Dana-Farber Cancer Institute in Boston describe their process in the 28 Dec. 2022 issue of Proceedings of the National Academy of Sciences<\/em><\/a> (paid subscription required).<\/p>\n

Mooney and colleagues are seeking ways to improve the clinical response of T-cells from the immune system, genetically altered to express chimeric antigen receptors<\/a>, also known as CAR T-cells. These engineered T-cells are designed to help find and destroy cancer cells that would normally evade attack by the immune system. CAR T-cells have so far produced mixed results in treating cancer patients, with somewhat greater success as a therapy for blood-related cancers such as lymphoma, than solid-tumor cancers. With solid tumors, CAR T-cells are still limited by the tumor microenvironment<\/a>, a network of tissue and blood cells that protects tumors.<\/p>\n

A technique for enhancing CAR T-cells is further engineering the cells by adding cytokines, enzymes in the immune system with cancer-killing properties. While technically possible, adding cell-destroying cytokines directly to T-cells, say the authors, increases risks of serious adverse effects in patients, making the approach not feasible under most conditions. Mooney’s lab<\/a> at Harvard’s engineering school and Wyss Institute studies biomaterials that affect cell and tissue functions, including design of new materials for aiding cancer therapies.<\/p>\n

The team led by Yutong Liu<\/a>, a doctoral candidate in Mooney’s lab, adapted methods from nanotechnology and chemistry to add cytokines to CAR T-cells in low, safe doses, by leveraging cells’ natural metabolism of sugar. The researchers first deliver a chemically reactive type of sugar with nanoscale particles to T-cells in lab cultures. The team then uses click chemistry<\/a>, techniques for identifying or designing molecular connections, to link modified cytokine molecules to the reactive sugar residing in the T-cells. Discoverers of click chemistry won the 2022 Nobel Prize for chemistry<\/a>.<\/p>\n

Compatible with today’s cell manufacturing techniques<\/h4>\n

This method for adding cytokines, say the authors, allows for localized delivery of the cancer-killing enzymes, making them safer for patients. “Only having to add sugar-containing nanoparticles and later the cytokines to the culture media,” says Liu in a Wyss Institute statement<\/a>, “makes the method extremely simple and fully compatible with the adoptive cell manufacturing pipeline.”<\/p>\n

The team tested their technique with lab mice induced with the aggressive skin cancer melanoma, using engineered CAR T-cells enhanced with the anti-tumor cytokine interleukin-12<\/a>. Results show enhanced CAR T-cells delay progression of melanoma tumors and extend mice lifetimes by 50 percent, with doses that would be too low to be effective for non-enhanced CAR T-cells. Findings also show a broader immune response, with a wider variety of immune system cells generated in test animals.<\/p>\n

The researchers also tested the technique in mice induced with the blood cancer lymphoma. Those results show CAR T-cells enhanced with interleuken-12 cytokines stopped the progression of lymphoma cells and extended lifetimes in test mice, also in doses that would be too low to be effective if not enhanced.<\/p>\n

The authors believe their techniques can be adapted quickly for clinical use. “Our approach,” notes Mooney, “can be easily scaled and integrated with the processes currently used to manufacture therapeutic T-cells, including CAR T-cells, and thus could have a relatively short path into clinical application.” The authors report the university applied for patents on the technology with Liu and Mooney among the inventors.<\/p>\n

More from Science & Enterprise:<\/p>\n