A recent study reveals the potential of using genetically modified NK cells in stem cell-derived therapy to target and treat treatment-resistant liver cancer more efficiently, opening up new approaches in the field of immunotherapy.
Researchers at the University of California San Diego have discovered a novel approach to tackle hepatocellular carcinoma (HCC), a type of liver cancer known for its resistance to conventional treatments. The method involves modifying natural killer (NK) cells, which are immune cells that can effectively eliminate tumor cells.
Unlike personalized chimeric antigen receptor (CAR)-T cell therapy, genetically modified NK cell therapy can be produced in large quantities and readily used for patients without the need for customization, as highlighted in the study published in Cell Stem Cell.
Professor Dan Kaufman, M.D., Ph.D., from UC San Diego School of Medicine explained, “Tumor cells, especially hepatocellular carcinoma, have mechanisms that suppress immune cells aiming to destroy them. This immune evasion is a significant challenge in treating solid tumors compared to blood cancers.”
The research team engineered stem cell-derived NK cells by disabling the receptor responsible for transforming growth factor beta (TGF-β), a protein that hinders immune responses. By doing so, they observed enhanced anti-tumor activity against HCC, a cancer type notorious for its low survival rates.
When comparing the modified NK cells with regular NK cells, Professor Kaufman noted, “The modified NK cells exhibited potent anti-tumor responses and prolonged survival rates in animal studies,” underscoring the importance of blocking TGF-β for improving the efficacy of immunotherapies.
Professor Kaufman expects that this breakthrough will have a ripple effect in advancing clinical trials across various research groups and companies working on immunotherapies for solid tumors, not limited to liver cancer but also applicable to other challenging malignancies.
Co-authors of the study include Jaya Lakshmi Thangaraj, Michael Coffey, and Edith Lopez from the Division of Regenerative Medicine at UC San Diego’s School of Medicine. The research was supported by NIH/NCI grants U01CA217885, P30CA023100 (administrative supplement), and the Sanford Stem Cell Institute at the University of California San Diego.
