Oncotarget

Research Papers:

Nanoparticle T cell engagers for the treatment of acute myeloid leukemia

Kinan Alhallak, Jennifer Sun, Barbara Muz, Amanda Jeske, Jessica Yavner, Hannah Bash, Chaelee Park, Berit Lubben, Ola Adebayo, Samuel Achilefu, John F. DiPersio and Abdel Kareem Azab _

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Oncotarget. 2021; 12:1878-1885. https://doi.org/10.18632/oncotarget.28054

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Abstract

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

Correspondence to:

Abdel Kareem Azab, email: kareem.azab@wustl.edu

Keywords: acute myeloid leukemia; T cell engagers; nanoparticles; 3D tissue culture model

Received: July 26, 2021     Accepted: August 13, 2021     Published: September 14, 2021

Copyright: © 2021 Alhallak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

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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