LAIR-1 agonism as a therapy for acute myeloid leukemia.

LAIR-1 agonism as a therapy for acute myeloid leukemia.

The Journal of clinical investigation (2023-11-15)

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

PMID37966113

摘要

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.

材料

货号

品牌

产品描述

SML0810

Sigma-Aldrich

MHY1485, ≥95% (HPLC)

218826

Sigma-Aldrich

Caspase-3/7 Inhibitor I, The Caspase-3/7 Inhibitor I, also referenced under CAS 220509-74-0, controls the biological activity of Caspase-3/7. This small molecule/inhibitor is primarily used for Cancer applications.