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LAIR-1 agonism as a therapy for acute myeloid leukemia
- Source :
- Journal of Clinical Investigation. November 15, 2023, Vol. 133 Issue 22
- Publication Year :
- 2023
-
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 venetodaxto establish LAIR-1 targeting as a therapeutic strategy for AML that may synergize with standard-of-care therapies.<br />Introduction Acute leukemias are characterized by the uncontrolled production of malignant hematopoietic progenitors. Acute myeloid leukemia (AML) is the most common adult acute leukemia (1). While extensive research has led [...]
- Subjects :
- STEMCELL Technologies Inc.
Viral antibodies -- Health aspects -- Analysis
Collagen -- Analysis -- Health aspects
B cells -- Analysis -- Health aspects
Cancer -- Care and treatment
Diagnostic reagents industry -- Analysis -- Health aspects
Hematopoietic stem cells -- Health aspects -- Analysis
Apoptosis -- Analysis -- Health aspects
Antibodies -- Health aspects -- Analysis
Health care industry
Vanderbilt University. Medical Center
Subjects
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 133
- Issue :
- 22
- Database :
- Gale General OneFile
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.773841662
- Full Text :
- https://doi.org/10.1172/JCI169519