Study Title: CAR memory-like NK cells targeting the membrane proximal domain of mesothelin demonstrate promising activity in ovarian cancer
Publication: Science Advances
Dana-Farber Cancer Institute authors include: Rizwan Romee, MD, senior author; and Mubin Tarannum, PhD, KhanhLinh Dinh, and Juliana Vergara, MD, MMSc, co-first authors
Summary: Natural killer, or NK, cells endowed with memory-like abilities and armed with a novel chimeric antigen receptor (CAR) have generated encouraging results in experiments in epithelial ovarian cancer (EOC) cells. Compared to earlier studies, which targetted the far end of the mesothelin protein on EOC cells, the new CIML NK cells, whose CAR targets the portion of mesothelin closer to the membrane, produced superior antitumor activity in laboratory lines of EOC cells and in human EOC cells grafted onto animal models. Importantly, researchers observed that the new CAR CIML NK cells maintained their activity after being exposed to ascitic fluid from patients – a fluid that builds up in the abdomen and has a suppressive effect on the immune system. When researchers tested the new cells in an animal model of peritoneal cancer, the cells not only caused the cancer to recede but prevented it from spreading to major organs.
Impact: Based on their effectiveness against epithelial ovarian cancer in the lab and in animal models, the new version of memory-like CAR NK cells should be evaluated in patients with advanced forms of the disease who have few other options, researchers say.
Funding: The work was supported by Dana Farber/Harvard Cancer Center Ovarian Cancer SPORE grant (1P50CA240243-01A1), the Ted and Eileen Pasquarello Research Fund, Expert Miracles Foundation, the Robert A. and Renée E. Belfer Family Foundation, and philanthropic support to Senior Author Rizwan Romee, MD.
