Cord blood-derived natural killer cells engineered with a novel, highaffinity chimeric antigen receptor can eliminate acute myeloid leukemia cells with minimal C-type lectin-like molecule-1 expression
Year: 2026
Type: article
Abstract: CAR NK cell therapy is expected to be developed to treat acute myeloid leukemia (AML). C-type lectin-like molecule 1 (CLL-1) is a candidate target. However, AML cells with minimal CLL-1 expression (CLL-1dim) may not be eliminated by CAR NK cells. Here we demonstrate that cord blood (CB)-derived NK cells transduced with a novel high-affinity CAR that recognizes CLL-1 can eliminate CLL-1dim AML cells. A newly established anti- CLL-1 monoclonal antibody (mAb) designated as 2-23 exhibits a higher affinity for CLL- 1 than the widely used anti-CLL-1 mAb M26. CB-derived NK cells transduced with a CAR derived from 2-23, but not M26, killed CLL-1dim AML cells in vitro. Additionally, treatment with 2-23 CAR NK cells, but not M26 CAR NK cells, significantly enhanced the survival of the mice transplanted with CLL-1dim AML cells in vivo. Furthermore, in AML patient-derived xenograft models, the 2-23 CAR NK cells expanded robustly, persisted, and eradicated AML cells.
Source: Haematologica
Authors: Makiko Suga, Shuhei Kida, Yo Mizutani, Yosuke Kogue, Yuta Yamaguchi, Shunya Ikeda, Ryuhei Kawamoto, Mana Tachikawa, Tsubasa Seto, Hiroto Takekawa, Yuto Maehara, Kumi Shibata, Kazuhito Tsutsumi, Hiraku Murakami, Emiko Mizuta, Kyoko Yoshihara, Satoshi Yoshihara, Hirohisa Nakamae, Takafumi Nakao, Megumu Inoue, Shuji Ueda, Satoru Kosugi, Yasutaka Ueda, Hisashi Kato, Shinsuke Kusakabe, Hidenori Kasahara, Akihisa Hino, Jiro Fujita, Tomoaki Ueda, Michiko Ichii, Kentaro Fukushima, Naoki Hosen
Institutions: Osaka Minami Medical Center, Osaka City University, Osaka International Cancer Institute, Osaka University of Economics, The University of Osaka, Osaka University of Pharmaceutical Sciences, Osaka International University, Osaka Rosai Hospital, Kansai Rosai Hospital, Osaka University Hospital, Otemae Hospital, Hyogo University, Osaka City General Hospital, Itami City Hospital, Hyogo Prefectural Nishinomiya Hospital, Toyonaka Municipal Hospital
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,157
OpenAlex ID: W7222005492
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