Nanoparticle T cell engagers for the treatment of acute myeloid leukemia
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Kinan Alhallak1,2, Jennifer Sun1,2, Barbara Muz1, Amanda Jeske1, Jessica Yavner1, Hannah Bash1, Chaelee Park1, Berit Lubben1, Ola Adebayo1, Samuel Achilefu2,3, John F. DiPersio4 and Abdel Kareem Azab1,2
1 Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA
2 Department of Biomedical Engineering, Washington University McKelvey School of Engineering, St. Louis, MO 63130, USA
3 Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA
4 Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
|Abdel Kareem Azab,||email:||[email protected]|
Keywords: acute myeloid leukemia; T cell engagers; nanoparticles; 3D tissue culture model
Received: July 26, 2021 Accepted: August 13, 2021 Published: September 14, 2021
Acute myeloid leukemia (AML) is the most common type of leukemia and has a 5-year survival rate of 25%. The standard-of-care for AML has not changed in the past few decades. Promising immunotherapy options are being developed for the treatment of AML; yet, these regimens require highly laborious and sophisticated techniques. We create nanoTCEs using liposomes conjugated to monoclonal antibodies to enable specific binding. We also recreate the bone marrow niche using our 3D culture system and use immunocompromised mice to enable use of human AML and T cells with nanoTCEs. We show that CD33 is ubiquitously present on AML cells. The CD33 nanoTCEs bind preferentially to AML cells compared to Isotype. We show that nanoTCEs effectively activate T cells and induce AML killing in vitro and in vivo. Our findings suggest that our nanoTCE technology is a novel and promising immuno-therapy for the treatment of AML and provides a basis for supplemental investigations for the validation of using nanoTCEs in larger animals and patients.
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