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

Abstract

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 in vitro and in vivo cancer cell growth.

• Authors: Daniele Bellavia, Stefania Raimondo, Giovanna Calabrese, Stefano Forte, Marta Cristaldi, Agostina Patinella, Lorenzo Memeo, Mauro Manno, Samuele Raccosta, Patrizia Diana, Girolamo Cirrincione, Gianluca Giavaresi, Francesca Monteleone, Simona Fontana, Giacomo De Leo, Riccardo Alessandro
• Journal: Theranostics (Theranostics) Vol. 7 Issue 5 Pg. 1333-1345 ( 2017) ISSN: 1838-7640 [Electronic] Australia
• PMID: 28435469 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Drug Carriers
• Receptors, Interleukin-3
• Imatinib Mesylate

Topics

• Animals
• Antineoplastic Agents (administration & dosage, pharmacokinetics)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Disease Models, Animal
• Drug Carriers (metabolism)
• Exosomes (metabolism)
• HEK293 Cells
• Heterografts
• Humans
• Imatinib Mesylate (administration & dosage, pharmacokinetics)
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy)
• Mice
• Receptors, Interleukin-3 (metabolism)
• Treatment Outcome