LAIR-1 agonism as a therapy for acute myeloid leukemia

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 ag...

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Detalles Bibliográficos
Autores principales: Lovewell, Rustin R., Hong, Junshik, Kundu, Subhadip, Fielder, Carly M., Hu, Qianni, Kim, Kwang Woon, Ramsey, Haley E., Gorska, Agnieszka E., Fuller, Londa S., Tian, Linjie, Kothari, Priyanka, Paucarmayta, Ana, Mason, Emily F., Meza, Ingrid, Manzanarez, Yanira, Bosiacki, Jason, Maloveste, Karla, Mitchell, Ngan, Barbu, Emilia A., Morawski, Aaron, Maloveste, Sebastien, Cusumano, Zac, Patel, Shashank J., Savona, Michael R., Langermann, Solomon, Myint, Han, Flies, Dallas B., Kim, Tae Kon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2023
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10650974/
https://www.ncbi.nlm.nih.gov/pubmed/37966113
http://dx.doi.org/10.1172/JCI169519
Descripción
Sumario: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.

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