Memory-like NK cell differentiation, inhibitory NKG2A blockade, and improved recognition via antibody or CAR engineering combine to enhance NK cell attack against multiple myeloma.

ABSTRACT: Natural killer (NK) cells are a promising approach for cellular cancer immunotherapy and are being investigated to treat patients with multiple myeloma (MM). We found that MM patient blood NK cell frequencies were normal with increased activating receptors and cytotoxic granules, without evidence of functional exhaustion. Despite this activated state, MM target cells were resistant to conventional NK cells by unclear mechanisms. Memory-like (ML) NK cells are generated after brief activation via the interleukin (IL)-12, IL-15, and IL-18 receptors and exhibit multiple enhanced antitumor properties. ML NK cell differentiation improved healthy donor and MM patient NK cell responses against MM target cells, in vitro and in vivo in immunodeficient murine xenograft models. Moreover, incorporating

SUBMITTER: Zhou AY 

PROVIDER: S-EPMC11844139 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature