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
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.
Authors
- Jiro Fujita (ORCID: https://orcid.org/0000-0003-3423-8343)
- Yosuke Kogue (ORCID: https://orcid.org/0009-0003-6839-9310)
- Takafumi Nakao
- Satoru Kosugi (ORCID: https://orcid.org/0000-0001-9057-5761)
- Hidenori Kasahara (ORCID: https://orcid.org/0000-0002-8349-4362)
- Megumu Inoue
- Kumi Shibata (ORCID: https://orcid.org/0009-0004-4034-5924)
- Tomoaki Ueda (ORCID: https://orcid.org/0000-0001-8806-5498)
- Yuto Maehara
- Kazuhito Tsutsumi
- Hiraku Murakami
- Makiko Suga (ORCID: https://orcid.org/0009-0002-5487-1525)
- Shinsuke Kusakabe (ORCID: https://orcid.org/0000-0002-9814-7611)
- Naoki Hosen (ORCID: https://orcid.org/0000-0001-9570-0947)
- Akihisa Hino (ORCID: https://orcid.org/0000-0002-7331-2713)
- Shuji Ueda (ORCID: https://orcid.org/0000-0002-4812-5625)
- Ryuhei Kawamoto
- Kentaro Fukushima (ORCID: https://orcid.org/0000-0002-8003-2584)
- Michiko Ichii (ORCID: https://orcid.org/0000-0002-0018-6656)
- Hisashi Kato (ORCID: https://orcid.org/0000-0003-4395-8369)
- Yuta Yamaguchi (ORCID: https://orcid.org/0000-0002-8314-9294)
- Hirohisa Nakamae (ORCID: https://orcid.org/0000-0003-4203-990X)
- Satoshi Yoshihara (ORCID: https://orcid.org/0000-0002-8537-2422)
- Hiroto Takekawa
- Yasutaka Ueda (ORCID: https://orcid.org/0000-0003-1562-1013)
- Shuhei Kida (ORCID: https://orcid.org/0000-0003-3906-3757)
- Yo Mizutani
- Emiko Mizuta
- Mana Tachikawa
- Kyoko Yoshihara (ORCID: https://orcid.org/0009-0001-9578-4850)
- Tsubasa Seto
- Shunya Ikeda
Institutions
- Osaka University of Economics (JP)
- Osaka City University (JP)
- Toyonaka Municipal Hospital (JP)
- Osaka City General Hospital (JP)
- Osaka Rosai Hospital (JP)
- Kansai Rosai Hospital (JP)
- Osaka Minami Medical Center (JP)
- Itami City Hospital (JP)
- Osaka International Cancer Institute (JP)
- Hyogo Prefectural Nishinomiya Hospital (JP)
- Osaka University Hospital (JP)
- Otemae Hospital (JP)
- Osaka International University (JP)
- Hyogo University (JP)
- Osaka University of Pharmaceutical Sciences (JP)
- The University of Osaka (JP)
Publication Details
- Journal
- Haematologica
- Published
- 2026-10-15
- DOI
- https://doi.org/10.3324/haematol.2026.301327
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 0.00