김태곤 (Vanderbilt University Medical Center)

한빛사논문

조회268

Vanderbilt University Medical Center

CV File 208 kb

J. Clin. Invest., Nov 15 2023, 133 (22) e169519 | https://doi.org/10.1172/JCI169519 LAIR-1 agonism as a therapy for acute myeloid leukemia

Rustin R. Lovewell,¹ Junshik Hong,^2,3,4 Subhadip Kundu,¹ Carly M. Fielder,² Qianni Hu,² Kwang Woon Kim,² Haley E. Ramsey,² Agnieszka E. Gorska,² Londa S. Fuller,² Linjie Tian,¹ Priyanka Kothari,¹ Ana Paucarmayta,¹ Emily F. Mason,⁵ Ingrid Meza,¹ Yanira Manzanarez,¹ Jason Bosiacki,¹ Karla Maloveste,¹ Ngan Mitchell,¹ Emilia A. Barbu,¹ Aaron Morawski,¹ Sebastien Maloveste,¹ Zac Cusumano,¹ Shashank J. Patel,¹ Michael R. Savona,^2,6,7,8 Solomon Langermann,¹ Han Myint,¹ Dallas B. Flies,¹ and Tae Kon Kim^2,5,6,7,8,9

¹NextCure Inc., Beltsville, Maryland, USA.

²Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

³Seoul National University Hospital and

⁴Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.

⁵Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center,

⁶Vanderbilt Center for Immunobiology,

⁷Vanderbilt-Ingram Cancer Center, and

⁸Program in Cancer Biology, Vanderbilt University, Nashville, Tennessee, USA.

⁹Veterans Affairs Tennessee Valley Healthcare, Nashville, Tennessee, USA.

Address correspondence to: Dallas B. Flies, Tae Kon Kim

Authorship note: RRL and JH contributed equally to this work as co–first authors.

DBF and TKK contributed equally to this work as co–senior and corresponding authors.

Abstract

Effective eradication of leukemic stem cells (LSCs) remains the greatest challenge in treating acute myeloid leukemia (AML). The immune receptor LAIR-1 has been shown to regulate LSC survival; however, the therapeutic potential of this pathway remains unexplored. We developed a therapeutic LAIR-1 agonist antibody, NC525, that induced cell death of LSCs, but not healthy hematopoietic stem cells in vitro, and killed LSCs and AML blasts in both cell- and patient-derived xenograft models. We showed that LAIR-1 agonism drives a unique apoptotic signaling program in leukemic cells that was enhanced in the presence of collagen. NC525 also significantly improved the activity of azacitidine and venetoclax to establish LAIR-1 targeting as a therapeutic strategy for AML that may synergize with standard-of-care therapies.

논문정보

형식Research article
게재일2023년 11월 (BRIC 등록일 2023-11-28)
연구진국내+국외 연구진
분야 의약학 > 응용의학

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