New research unveils a powerful tool to boost natural killer cell therapies.
A new study from The University of Texas MD Anderson Cancer Center (TX, USA) has revealed that natural killer (NK) cells can become significantly more effective at destroying cancer cells when specific genes are removed. The research introduces PreCiSE — a novel genome-wide CRISPR screening platform specifically optimized for NK cells that identifies key genetic targets to enhance their anti-cancer properties.
“Targeted gene editing is a powerful tool to enhance the anticancer activity of NK cells,” said Katy Rezvani, professor of Stem Cell Transplantation and Cellular Therapy and vice president and head of the Institute for Cell Therapy Discovery & Innovation at MD Anderson. “PreCiSE is more than a screening tool. It is a roadmap that reveals how tumors suppress our cells and how to reengineer CAR NK cells to resist those pressures across many cancer types.”
The research team, led by Rezvani along with co-first authors Alexander Biederstaedt and Rafet Basar, developed PreCiSE to uncover multiple checkpoints and pathways that regulate NK cell activity when confronted with the immunosuppressive tumor microenvironment.
By systematically identifying and removing these genetic targets, researchers observed remarkable improvements in NK cell function, including:
• Enhanced innate and CAR-mediated NK cell activity
• Improved metabolic fitness
• Increased production of pro-inflammatory cytokines
• Expansion of cytotoxic NK cell subsets
Most importantly, these enhanced NK cells demonstrated effectiveness even in cancer models that had become resistant to treatment.
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While the study validated three specific targets — MED12, ARIH2, and CCNC — the implications extend far beyond individual genes. The PreCiSE platform provides researchers with a comprehensive map of NK cell regulators that can be prioritized, edited and combined to design more effective CAR NK cell therapies.
Interestingly, some of the identified regulators overlap with pathways already known in T cell biology, while others appear to be NK-specific. This highlights the value of developing a platform specifically tailored to NK cells rather than relying on insights from T cell research.
“This has given us significant insight into the next generation of cell therapies that have the potential to be more powerful, precise and resistant to cancer,” Rezvani noted.
As research continues, the PreCiSE platform may accelerate the development of more effective immunotherapies, offering new hope for patients with difficult-to-treat cancers and potentially transforming the landscape of cancer treatment.