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Jennifer R. Brown, MD, PhD


Membrane-Bound IL-21–Expanded NK Cells Under Study in CLL

By: Amy MacDonald, MS
Posted: Tuesday, October 25, 2022

In an article in the journal Blood Advances, co-senior authors John C. Byrd, MD, and Natarajan Muthusamy, PhD, DVM, both of The Ohio State University, Columbus, and colleagues demonstrated that both healthy donor-derived natural killer (NK) cells as well as those from patients with chronic lymphocytic leukemia (CLL) expanded rapidly when stimulated with feeder cells expressing membrane-bound interleukin-21 (IL-21). These investigational cells showed cytotoxic activity against allogeneic or autologous CLL cells in vitro. They also were efficacious in vivo in combination with anti-CD20 antibodies and venetoclax.

Current treatment for CLL involves the anti-CD20 antibody obinutuzumab, the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib, and often the BH3-mimetic venetoclax. Although NK cells are activated by these antitumor agents, they are not present in sufficient numbers to be therapeutically relevant. Thus, this new method of ex vivo NK cell expansion using membrane-bound IL‐21–expressing feeder cells and IL-2 was found to be effective at generating large quantities of NK cells. The investigators, including first author Max Yano, MD-PhD student, assessed the suitability of combining these expanded NK cells with current treatment for CLL.

Both healthy donor‐derived and NK cells from patients with CLL were assessed following membrane-bound IL‐21–mediated expansion and found to have cytotoxic activity against both allogeneic and autologous CLL cells. Of note, despite the immune suppression present in patients with CLL, patients’ NK cells were able to be expanded in quantities similar to those from healthy donors. Moreover, membrane-bound IL-21–expanded NK cells were compatible with both venetoclax and obinutuzumab in two CLL xenograft mouse models. Venetoclax did not alter NK counts or in vivo NK activation, and ibrutinib did not alter NK cell expansion or activity against autologous CLL cells.

Collectively, these data support investigating the addition of membrane-bound IL-21–expanded NK cells to conventional obinutuzumab and venetoclax therapy for patients with CLL.

Disclosure: For full disclosures of study authors, visit

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