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Targeted Killing of Monocytes/Macrophages and Myeloid Leukemia Cells with Pro-Apoptotic Peptides

1
Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Ullernchausseen 70, N0379 Oslo, Norway
2
Department of Haematology, Oslo University Hospital-Rikshospitalet, Sognsvannvien 20, N0372 Oslo, Norway
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(8), 1088; https://doi.org/10.3390/cancers11081088
Received: 18 April 2019 / Revised: 22 July 2019 / Accepted: 26 July 2019 / Published: 31 July 2019
(This article belongs to the Special Issue Immunotherapy, Tumor Microenvironment and Survival Signaling)
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Abstract

Several cells of myeloid origin, such as monocytes and macrophages are involved in various human disorders, including cancer and inflammatory diseases. Hence, they represent attractive therapeutic targets. Here we developed three lytic hybrid peptides, by fusing a monocyte- and macrophage-binding peptide to pro-apoptotic peptides, and investigated their killing potency on blood monocytes, macrophages, and leukemia cells. We first showed that the targeting NW peptide is effective for depleting monocytes from whole peripheral blood mononuclear cells (PBMCs). Incubating the cells with biotin-conjugated NW peptide, and the subsequent capture on streptavidin-conjugated magnetic beads, depleted monocytes from the PBMCs. The NW peptide also depleted myeloid leukemia blasts from patient PBMCs. The treatment of the PBMCs with the lytic hybrid NW-KLA peptide killed monocytes, but not lymphocytes and primary mammary epithelial cells. Additionally, the fusion peptide exhibited a potent toxicity against macrophages and leukemia cells. The free lytic KLA peptide did not affect cells. Similarly, a second lytic hybrid peptide killed macrophages, leukemia cell lines, and blood leukemia blasts from patients with acute and chronic myeloid leukemia. The IC50 towards target cells were in the low macromolar range (4–12 µM). Overall, the data indicate that the NW peptide could be a potential drug delivery agent for monocytes, macrophages, and leukemia cells. Moreover, the engineered lytic hybrid peptides acting alone, or in combination with other therapeutic agents, might benefit many cancer patients and overcome drug resistance. View Full-Text
Keywords: tumor microenvironment; macrophages; leukemia cells; lytic peptides; targeted therapy; immunotherapy; cancer tumor microenvironment; macrophages; leukemia cells; lytic peptides; targeted therapy; immunotherapy; cancer
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Sioud, M.; Pettersen, S.; Ailte, I.; Fløisand, Y. Targeted Killing of Monocytes/Macrophages and Myeloid Leukemia Cells with Pro-Apoptotic Peptides. Cancers 2019, 11, 1088.

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