Researchers at The University of Texas MD Anderson Cancer Center have developed a novel tool that significantly improves the effectiveness of natural killer (NK) cell therapies in combatting cancer. The new genome-wide CRISPR screening platform, named PreCiSE, enhances the ability of CAR NK cells to target and destroy cancer cells by identifying key gene targets for modification.
The findings, published in the esteemed journal Cancer Cell, indicate that by removing certain gene targets, NK cells exhibit a marked increase in their cancer-fighting capabilities. This advancement could pave the way for more effective therapies against various types of cancer.
Katy Rezvani, M.D., Ph.D., the study’s corresponding author and a professor of Stem Cell Transplantation and Cellular Therapy, noted, “Targeted gene editing is a powerful tool to enhance the anticancer activity of NK cells.” Rezvani serves as the vice president and head of the Institute for Cell Therapy Discovery & Innovation at MD Anderson.
Insights into Tumor Suppression
The research team, led by Rezvani and co-first authors Alexander Biederstaedt, M.D., and Rafet Basar, M.D., Ph.D., utilized PreCiSE to uncover multiple checkpoints and pathways that regulate NK cell activity. This process revealed how tumor environments suppress immune responses. The study found that by editing specific gene targets, researchers could enhance both innate and CAR-mediated NK cell functions, leading to improved metabolic fitness, increased pro-inflammatory cytokine production, and the expansion of cytotoxic NK cell subsets in cancer models that had previously shown resistance to treatment.
Among the validated targets identified in the study are three significant genes: MED12, ARIH2, and CCNC. These genes not only play critical roles in NK cell biology but also intersect with pathways known to be important for T cells, emphasizing the comprehensive nature of the PreCiSE platform.
Future Directions for Cell Therapies
The implications of this research extend beyond the identified genes. PreCiSE serves as a comprehensive map of NK cell regulators, allowing for a more strategic approach in designing CAR NK cell therapies. The study validated these key targets in vivo across multiple tumor models, confirming their relevance in the context of immune suppression.
Rezvani expressed optimism about the potential of these findings, stating, “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.” The Rezvani Laboratory has been at the forefront of engineered NK cell therapy and is actively progressing CAR NK approaches into clinical trials for patients battling advanced hematologic and solid malignancies.
The research was supported by various philanthropic contributions to the Institute for Cell Therapy Discovery & Innovation, including significant commitments from organizations and foundations such as the Marcus Foundation, Inc. and the National Institutes of Health, among others.
As the study indicates, the current findings will play a crucial role in enhancing the efficacy and activity of CAR NK cells against a broader range of cancer types, ultimately aiming to improve patient outcomes in the fight against cancer.