Interleukin 3- receptor targeted exosomes inhibit in vitro and in vivo Chronic Myelogenous Leukemia cell growth

Despite Imatinib (IM), a selective inhibitor of Bcr-Abl, having led to improved prognosis in Chronic Myeloid Leukemia (CML) patients, acquired resistance and long-term adverse effects is still being encountered. There is, therefore, urgent need to develop alternative strategies to overcome drug resi...

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Bibliographic Details
Published in:Theranostics 2017-01, Vol.7 (5), p.1333-1345
Main Authors: Bellavia, Daniele, Raimondo, Stefania, Calabrese, Giovanna, Forte, Stefano, Cristaldi, Marta, Patinella, Agostina, Memeo, Lorenzo, Manno, Mauro, Raccosta, Samuele, Diana, Patrizia, Cirrincione, Girolamo, Giavaresi, Gianluca, Monteleone, Francesca, Fontana, Simona, De Leo, Giacomo, Alessandro, Riccardo
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - pharmacokinetics
Cell Line, Tumor
Cell Proliferation - drug effects
Disease Models, Animal
Drug Carriers - metabolism
Exosomes - metabolism
HEK293 Cells
Heterografts
Humans
Imatinib Mesylate - administration & dosage
Imatinib Mesylate - pharmacokinetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy
Mice
Receptors, Interleukin-3 - metabolism
Research Paper
Treatment Outcome
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Summary:Despite Imatinib (IM), a selective inhibitor of Bcr-Abl, having led to improved prognosis in Chronic Myeloid Leukemia (CML) patients, acquired resistance and long-term adverse effects is still being encountered. There is, therefore, urgent need to develop alternative strategies to overcome drug resistance. According to the molecules expressed on their surface, exosomes can target specific cells. Exosomes can also be loaded with a variety of molecules, thereby acting as a vehicle for the delivery of therapeutic agents. In this study, we engineered HEK293T cells to express the exosomal protein Lamp2b, fused to a fragment of Interleukin 3 (IL3). The IL3 receptor (IL3-R) is overexpressed in CML blasts compared to normal hematopoietic cells and thus is able to act as a receptor target in a cancer drug delivery system. Here we show that IL3L exosomes, loaded with Imatinib or with BCR-ABL siRNA, are able to target CML cells and inhibit and cancer cell growth.
ISSN:1838-7640
1838-7640
DOI:10.7150/thno.17092