Advancements in CRISPR Screening Enhance CAR NK Cell Cancer Therapies

Innovative CRISPR screening has identified key genetic targets that can improve the efficacy of CAR NK cell therapies against multiple cancer types, opening new avenues for cancer immunotherapy.
Recent research from the University of Texas MD Anderson Cancer Center has demonstrated significant progress in the field of immunotherapy by utilizing genome-wide CRISPR screening to identify critical genetic targets that boost the effectiveness of natural killer (NK) cell-based cancer treatments. Through an innovative platform called PreCiSE, optimized specifically for primary human NK cells, scientists uncovered multiple checkpoints and pathways that regulate NK cell activity within the tumor microenvironment, which often employs various mechanisms to suppress immune responses.
The study revealed that editing key genes, such as MED12, ARIH2, and CCNC, enhances NK cell cytotoxicity, metabolic resilience, and cytokine production, enabling these cells to better combat different cancer types even under immune-suppressive conditions. Notably, some regulators like MED12 and CCNC are linked to pathways also involved in T cell biology, while others like ARIH2 appear to be NK-specific, highlighting the platform's capability to identify unique and overlapping immune pathways.
This research underscores the potential of targeted gene editing to create more powerful and resistant CAR NK cells, paving the way for improved therapies for hematologic and solid tumors. The findings, published in Cancer Cell, also demonstrate the validation of these genetic targets in vivo, in multiple tumor models, supporting their clinical relevance.
Kitty Rezvani, M.D., Ph.D., leading the study, emphasizes that PreCiSE not only functions as a deep screening tool but also as a strategic roadmap for designing next-generation cell therapies. The ongoing development of this technology aims to overcome immune resistance mechanisms and extend the benefits of NK cell therapies to more patients. With prior advancements by Rezvani’s team in engineered NK cells entering clinical trials, these new insights are expected to significantly enhance the efficacy of future treatments in combating various cancers.
Source: https://medicalxpress.com/news/2025-08-crispr-screening-key-car-nk.html
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