UCSD Team Tests Stem Cell-Derived Therapy On Liver Cancer; Results Promising

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07/30/2024

UC San Diego scientists have found the most common form of liver cancer could be targeted and treated more effectively using a stem cell-derived therapy, according to a report published Tuesday.

The report, published in the scientific journal Cell Stem Cell, focuses on hepatocellular carcinoma, a cancer with a high mortality rate.

While not yet studied in patients, the treatment — which involves the lab engineering of “natural killer” white blood cells to battle HCC — could be mass-produced and ready for deployment rapidly, the researchers said.

Unlike a treatment called chimeric antigen receptor-expressing T-cell therapy, which requires patient personalization, the NK-cell therapy could be more acceptable to more bodies.

“To some extent all tumor cells — perhaps hepatocellular carcinoma more so — inhibit immune cells that try to kill them,” said UCSD School of Medicine Professor Dr. Dan Kaufman, lead author on the study and director of the Sanford Advanced Therapy Center at the university’s Sanford Stem Cell Institute and Moores Cancer Center member.

“This is one key reason why some immunotherapies like CAR T cells have been less successful for solid tumors than for blood cancers — the immunosuppressive tumor microenvironment.”

Kaufman and his team produced the NK cells in which a protein that impairs immune function was disabled. Hepatocellular carcinoma tumors and the liver in general contain large amounts of the substance, which both inhibits the immune cell activity and allows cancer to proliferate, the authors write.

Typical NK cells without the disabled receptor, like CAR T cells, were not very effective in battling the cancer.

“These are pretty resistant tumors — when we put them in mice, they grow and kill the mice,” Kaufman said.

The five-year survival rate for HCC in humans is less than 20% and is responsible for more than 12,000 deaths in the United States annually.

However, when researchers tested the modified NK cells against the cancer, “we got very good anti-tumor activity and significantly prolonged survival.”

“These studies demonstrate that it is crucial to block transforming growth factor beta — at least for NK cells, but I also think it’s true for CAR T cells,” Kaufman said. “If you unleash NK cells by blocking this inhibitory pathway, they should kill cancer quite nicely.”

He said his team’s discovery will likely be reflected in clinical trials for many groups working with the various therapies or solid tumors.

— City News Service, Inc.

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