Ron DePinho, Professor and Past President of MD Anderson Cancer Center, shared a post on LinkedIn about a paper by Katayoun Rezvani et al. published in Cancer Cell:
“A new elegant study from CAR-NK pioneer Katy Rezvani, MD Anderson Cancer Center leverages genome-wide CRISPR screening in primary human NK cells to map the key genetic regulators that constrain NK cell function within the tumor microenvironment.
Impressively, the screens identified MED12, CCNC, and ARIH2 as druggable checkpoints whose loss markedly enhances NK antitumor activity. Strikingly, dual knockout of ARIH2 and CCNC in CAR-NK cells further boosted in vivo efficacy—highlighting a strategy to increase metabolic fitness, cytokine production, and expansion of cytotoxic NK subsets.
This work provides a valuable blueprint for rational engineering of next-generation NK and CAR-NK therapies capable of overcoming tumor-induced immunosuppression.
Another great step forward for the field of cellular immunotherapy.”
Title: Genome-wide CRISPR screens identify critical targets to enhance CAR-NK cell antitumor potency
Authors: Alexander Biederstädt, Rafet Basar, Jeong-Min Park, Nadima Uprety, Rejeena Shrestha, Francia Reyes Silva, Merve Dede, John Watts, Sunil Acharya, Donghai Xiong, Bin Liu, May Daher, Hind Rafei, Pinaki Banerjee, Ping Li, Sanjida Islam, Huihui Fan, Mayra Shanley, Jingling Jin, Bijender Kumar, Vernikka Woods, Paul Lin, Silvia Tiberti, Ana Karen Nunez Cortes, Xin Ru Jiang, Inci Biederstädt, Patrick Zhang, Ye Li, Seema Rawal, Enli Liu, Luis Muniz-Feliciano, Gary M. Deyter, Elizabeth J. Shpall, Natalie Wall Fowlkes, Ken Chen, Katayoun Rezvani
You can read the full article in Cancer Cell.
More from Ron DePinho on OncoDaily.